Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used forma...Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.展开更多
Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the i...Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate ...The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 10<sup>7</sup> FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.展开更多
Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in ...Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.展开更多
Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving va...Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.展开更多
BACKGROUND Japanese encephalitis virus(JEV),a mosquito borne flavivirus,is the leading cause of viral encephalitis in Asia,in terms of frequency and severity.JEV infection is thought to confer lifelong immunity.With t...BACKGROUND Japanese encephalitis virus(JEV),a mosquito borne flavivirus,is the leading cause of viral encephalitis in Asia,in terms of frequency and severity.JEV infection is thought to confer lifelong immunity.With the near eradication of poliomyelitis,JEV is now the continent’s leading cause of childhood viral neurologic infection and disability.The most common clinical manifestation of JEV infection is acute encephalitis,and currently there is no specific antiviral therapy.Japanese Encephalitis Vaccine(JE-VC)is an effective prevention measure,including JE-VC,Live(JE-MB),and Inactivated JE-VC.CASE SUMMARY A 9-mo-old girl received injection of Inactivated JE-VC(Vero cell)(Liaoning Chengda,batch number 201611B17)on August 31,2017.On that night,she developed a fever with the body temperature up to 38.5°C,for which Ibuprofen Suspension Drops 1.25 mL was given as antipyretic treatment.On September 1,the patient developed apocleisis,and her parents noticed herpes in her oral cavity.The patient was sent to our hospital on September 3.Physical examination led to a diagnosis of herpetic stomatitis,for which Stomatitis Spray 1 puff,tid,Kangfuxin Liquid 2 mL,tid,and vitamin B20.5 tablet,tid,were prescribed.Routine blood tests for low fever on September 6,2017 revealed an absolute neutrophil count(ANC)of 0.62×109/L,hemoglobin(Hb)of 109 g/L,and platelet count(PLT)of 308×10^(12)/L,and the tests were monitored regularly thereafter.The patient was followed until July 26,2020,when routine blood tests revealed ANC 1.72×109/L,Hb 138 g/L,and PLT 309×1012/L,indicating that the neutropenia count had normalized.CONCLUSION This report attempts to bring to clinical attention that Inactivated JE-VC(Vero cell)might cause prolonged granulocytopenia or even agranulocytosis.展开更多
BACKGROUND With rapid and extensive administration of inactivated coronavirus disease 2019(COVID-19)vaccine to the general population in China,it is crucial for clinicians to recognize neurological complications or ot...BACKGROUND With rapid and extensive administration of inactivated coronavirus disease 2019(COVID-19)vaccine to the general population in China,it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination.CASE SUMMARY Here we report the first case of Bell’s palsy after the first dose of inactivated COVID-19 vaccine in China.The patient was a 36-year-old woman with a past history of Bell’s palsy.Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine,the patient developed right-side Bell’s palsy and binoculus keratoconjunctivitis.Prednisone,artificial tears and fluorometholone eye drops were applied.The patient’s symptoms began to improve by day 7 and resolved by day 54.CONCLUSION As mRNA COVID-19 vaccine trials reported cases of Bell’s palsy as adverse events,we should pay attention to the occurrence of Bell’s palsy after inactivated COVID-19 vaccination.A history of Bell’s palsy,rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell‘s palsy after COVID-19 vaccination.展开更多
We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging va...We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.展开更多
We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite their close kinship,SARS-CoV and Covid-19 ...We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(D)with Glycine(G)composes the D614G mutation that is around 20%more infectious than its predecessor 614D.The B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid exchange.We examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions involved.Unlike previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging vaccines.Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the cell.Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital organs.With respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version,the Adenovirus DNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that appears to demonstrate the greatest effectiveness,yet,encompass a relatively higher risk.展开更多
Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Th...Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.展开更多
Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines....Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines an...Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines and therapeutics against SFTSV currently.B‐Propiolactone(BPL)inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 adjuvant.The experimental SFTS vaccine was a satisfying immunogen,which could efficiently trigger the development of high levels of SFTSV NP‐specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice,and could induce SFTS virus‐specific cellular immune responses to a certain extent.A single dose of vaccine was immunogenically insufficient in BALB/c mice;the second and third dose resulted in significant boost in antibody response.The use of Al(OH)3 adjuvant resulted in higher antibody titers.The mediate‐dose of vaccine could induce as high and equivalent level of antibody titer as that of high‐dose.The experimental SFTS vaccine in mediate‐and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild‐type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with controls.The experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice,and could protect C57/BL6 mice against SFTS virus challenge.These results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.展开更多
Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiel...Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.展开更多
Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity a...Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.展开更多
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a ran...Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population.Methods: In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis.Results: A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0-14, 0-21, and 0-28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95%CI: 88.4-108.4) in the 0-14 group, which was significantly lower compared with 134.4 (95%CI: 123.1-145.7) in the 0-21 group (P < 0.001 vs 0-14 group) and 145.5 (95%CI: 131.3-159.6) in the 0-28 group (P < 0.001 vs 0-14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild.Conclusions: Both a two-dose of inactivated SARS-CoV-2 vaccine at 0-21 days and 0-28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0-14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%.展开更多
Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-s...Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response.To this end,a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted,and the participants were followed up at 3.3(Visit 1),9.2(Visit 2),and 18.5(Visit 3)months after SARS-CoV-2 infection.They were classified into three groups(no-vaccination(n=54),one-dose(n=62),and two-dose(n=92)groups)on the basis of the administration of inactivated vaccination.The neutralizing antibody(NAb)titers against the wild-type virus continued to decrease in the no-vaccination group,but they rose significantly in the one-dose and two-dose groups,with the highest NAb titers being observed in the two-dose group at Visit 3.The NAb titers against the Delta variant for the no-vaccination,one-dose,and two-dose groups decreased by 3.3,1.9,and 2.3 folds relative to the wild-type virus,respectively,and those against the Omicron variant decreased by 7.0,4.0,and 3.8 folds,respectively.Similarly,the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose.Results showed that the convalescents benefited from the administration of the inactivated vaccine(one or two doses),which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses.Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic,and vaccination guidelines and policies need to be updated.展开更多
Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from c...Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage.The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines.The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes.The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response.展开更多
Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant...Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines.In this study,we constructed a recombinant virus,rCVS11-LTB,which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit(LTB)protein on the surface of the RABV particles.Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells(DCs).Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virusneutralizing antibodies(VNAs)in both mice and dogs than the parent virus rCVS11,to enhance the cellular immune response and T cell immune memory in mice,and was also able to provide 100%protection in mice from lethal doses of rabies virus,indicating its potential as a safe and effective inactivated rabies vaccine candidate.展开更多
Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced...Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomic status,cultural beliefs,concerns about vaccine safety,and cost may hinder caregivers from vaccinating their children.Further measures,such as health education campaigns to raise knowledge and awareness,and encouragement of domestic vaccine innovation,which would reduce out-of-pocket costs,could be implemented to improve the coverage of DTap-IPV/Hib vaccination.展开更多
基金supported by the Fish Innovation Team of Shandong Agriculture Research System (No. SDAIT-1206)the Aquatic Animal Immunologic Agents Engineering Research Center of Shandong Province, the Qingdao Agricultural University Doctoral Start-Up Fund (6631122030)+5 种基金the National Natural Science Foundation of China (No. 32002421)the Advanced Talents Foundation of QAU (No. 6651118016)the Natural Science Foundation of Shandong Province (No. ZR2019BC009)the ‘First-Class Fishery Discipline’ program of Shandong Province, the special top talent plan ‘One Thing One Decision (Yi Shi Yi Yi)’the Key Research and Development Program in Shandong Province (No. 2018YFJH0703)Breeding Plan of Shandong Provincial Qingchuang Research Team (2019)
文摘Vibrio scophthalmi and Aeromonas salmonicida can cause high turbot mortality and huge economic losses.Presently,vaccination is the most promising method for preventing communicable diseases.In this study,we used formalin to kill V.scophthalmi and A.salmonicida cells,and mixed with the mineralized oil adjuvant(Montanide^(TM)ISA 763 AVG)to prepare the bivalent inactivated vaccine.The results showed that turbot inoculated with the bivalent inactivated vaccine exhibited strong tolerance to the infection of V.scophthalmi and A.salmonicida,and no obvious clinical symptoms and pathological changes were observed.The activities of enzymes lysozyme,acid phosphatase and complement C3 had significantly increased after the vaccination.The antibody titer response of vaccinated turbot was greatly boosted,which was positively connected with the immunological impact according to ELISA results.Simultaneously,the expression levels of immune-related genes such as MHC-IIα,MHC-IIβ,CD4,CD8,TNF-αand IL^(-1)βwere up-regulated,demonstrating that it might stimulate humoral and cellular immunological response in turbot.These findings highlight the potential of the bivalent inactivated vaccine for controlling V.scophthalmi and A.salmonicida infections in turbot.
基金by grants from the Guangdong Emergency Program for Prevention and Control of COVID-19(No.2020A1111340002)the Shenzhen Key Research Project for Prevention and Control of COVID-19.
文摘Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
文摘The upstream process was carried out in an animal component-free medium on Cytodex 1 microcarriers. Recombinant trypsin is a non-animal derived protease used as an alternative to animal-derived trypsin. To inactivate recombinant trypsin, a soybean trypsin inhibitor (STI) should be added to the medium. A protocol was first tested in T-flasks and then passaged to 500 mL and 3 L spinner flasks. Cell detachment was completed in 10 - 12 min, and 0.4 g/L STI was added to a 3L spinner, and cells were transferred into a 30 L stirred tank bioreactor. On day 5, the cell density had reached its maximum (around 1.8 × 106 cells/mL). At an MOI of 0.3 with serum-free medium conditions, cell infection yielded a maximal rabies virus titer of 1.82 × 10<sup>7</sup> FFU/mL at 5 days. All cell culture conditions and virus growth kinetics in serum-free media were investigated. In conclusion, Vero cells were grown on Cytodex 1 with serum-free media and a high amount of rabies virus was obtained. A mouse challenge was used to determine the immune response to an inactivated rabies virus vaccine candidate. Also, we evaluated inactive rabies vaccine candidate safety, and immunogenicity in mice, sheep, horses, and cattle. We found that no horses, sheep, or cattle who were given vaccine IM at 3.2 IU/dose exhibited any clinical sign of disease and all developed high VNA titers (up to 10.03 IU/mL) by 3 - 4 WPI. After the accelerated stability studies, the lyophilized inactivated rabies vaccine candidate showed enough antigenic potency (2.6 IU/mL) in the mouse challenge test. Also, 18-month long-term stability studies showed enough immune response (1.93 IU/mL) on day 14. The activity of the vaccine candidate showed a good immune response and safety criteria that meet WHO requirements. This is the first pilot-scale mammalian cell-based viral rabies vaccine production study in Türkiye that used microcarriers.
基金supported by grants from the Applied Basic Research Key Project of Wuhan Municipal Bureau of Science and Technology(No.2020020601012218)the Fundamental Research Funds for the Central Universities(HUST COVID-19 Rapid Response Call No.2020kfyXGYJ040)National Natural Science Foundation of China(No.81802090).
文摘Objective:The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates.To explore the influencing factors on vaccine-induced effects,antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.Methods:All subjects aged 18-60 years who did not have SARS-CoV-2 infection at the time of screening from June 19,2021,to July 02,2021,were approached for inclusion.All participants received two doses of inactivated SARS-CoV-2 vaccine.Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination.A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL.This retrospective study included 97 infection-naive individuals(mean age 35.6 years;37.1%male,62.9%female).Results:The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1%and 74.2%,respectively.IgG antibody levels were significantly higher than IgM levels(P<0.0001).Sex had no effect on IgM and IgG antibody response after the second dose.The mean anti-IgG level in older persons(≥42 years)was significantly lower than that of younger recipients.There was a significantly lower antibody level at>42 days compared to that at 0-20 days(P<0.05)and 21-31 days(P<0.05)after the second dose.Conclusion:IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals(>18 years),which can be influenced by age and detection time after the second dose of vaccination.
基金sub-project of National Major Scientific and Technological Special Project of China for‘Significant New Drugs Development’[2015ZX09501008-004]。
文摘Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune protection.Methods Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.Results A total of 375 participants who completed the two-dose vaccination were included in the analysis.Both models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix.Additionally,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 years.Moreover,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.Conclusions Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.
文摘BACKGROUND Japanese encephalitis virus(JEV),a mosquito borne flavivirus,is the leading cause of viral encephalitis in Asia,in terms of frequency and severity.JEV infection is thought to confer lifelong immunity.With the near eradication of poliomyelitis,JEV is now the continent’s leading cause of childhood viral neurologic infection and disability.The most common clinical manifestation of JEV infection is acute encephalitis,and currently there is no specific antiviral therapy.Japanese Encephalitis Vaccine(JE-VC)is an effective prevention measure,including JE-VC,Live(JE-MB),and Inactivated JE-VC.CASE SUMMARY A 9-mo-old girl received injection of Inactivated JE-VC(Vero cell)(Liaoning Chengda,batch number 201611B17)on August 31,2017.On that night,she developed a fever with the body temperature up to 38.5°C,for which Ibuprofen Suspension Drops 1.25 mL was given as antipyretic treatment.On September 1,the patient developed apocleisis,and her parents noticed herpes in her oral cavity.The patient was sent to our hospital on September 3.Physical examination led to a diagnosis of herpetic stomatitis,for which Stomatitis Spray 1 puff,tid,Kangfuxin Liquid 2 mL,tid,and vitamin B20.5 tablet,tid,were prescribed.Routine blood tests for low fever on September 6,2017 revealed an absolute neutrophil count(ANC)of 0.62×109/L,hemoglobin(Hb)of 109 g/L,and platelet count(PLT)of 308×10^(12)/L,and the tests were monitored regularly thereafter.The patient was followed until July 26,2020,when routine blood tests revealed ANC 1.72×109/L,Hb 138 g/L,and PLT 309×1012/L,indicating that the neutropenia count had normalized.CONCLUSION This report attempts to bring to clinical attention that Inactivated JE-VC(Vero cell)might cause prolonged granulocytopenia or even agranulocytosis.
基金Supported by Zhejiang Provincial Administration of Traditional Chinese Medicine,No.2020ZT001.
文摘BACKGROUND With rapid and extensive administration of inactivated coronavirus disease 2019(COVID-19)vaccine to the general population in China,it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination.CASE SUMMARY Here we report the first case of Bell’s palsy after the first dose of inactivated COVID-19 vaccine in China.The patient was a 36-year-old woman with a past history of Bell’s palsy.Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine,the patient developed right-side Bell’s palsy and binoculus keratoconjunctivitis.Prednisone,artificial tears and fluorometholone eye drops were applied.The patient’s symptoms began to improve by day 7 and resolved by day 54.CONCLUSION As mRNA COVID-19 vaccine trials reported cases of Bell’s palsy as adverse events,we should pay attention to the occurrence of Bell’s palsy after inactivated COVID-19 vaccination.A history of Bell’s palsy,rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell‘s palsy after COVID-19 vaccination.
文摘We examined the coronavirus classification and evolution through its multiple mutations that have increased its transmissibility rate up to 70% globally, threatening to undermine the promise of a number of emerging vaccines that primarily focus on the immune detection of the Spike trimer. The safety and effectiveness of different vaccination methods are evaluated and compared, including the mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, and the live attenuated coronavirus. Mutations have been long considered as random events, or mistakes during the viral RNA replication. Usually, what can go wrong will go wrong;therefore, repeated transformations lead to the extinction of a virus. On the contrary, the aggregate result of over 300,000 Covid-19 variants has expanded its transmissibility and infectiousness. Covid-19 mutations do not degrade the virus;they empower and facilitate its disguise to evade detection. Unlike other coronaviruses, Covid-19 amino acid switches do not reflect the random unfolding of errors that eventually eradicate the virus. Covid-19 appears to use mutations adaptively in the service of its survival and expansion. We cite evidence that Covid-19 inhibits the interferon type I production, compromising adaptive immunity from recognizing the virus. The deleterious consequences of the cytokine storm where the CD8+ killer cells injure the vital organs of the host may well be a Covid-19 manoeuvring to escape exposure. It is probable that evolution has programmed Covid-19 with an adeptness designed to debilitate key systemic defences to secure its subsistence. To date the infectiousness of the Covid-19 pandemic is exponentially increasing, denoting the possibility of an even more dangerously elusive, inconspicuous, and sophisticated version of the disease.
文摘We traced the coronavirus classification and evolution,analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.Despite their close kinship,SARS-CoV and Covid-19 display significant structural differences,including 380 amino acid substitutions,and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.A single amino acid substitution such as replacing Aspartate(D)with Glycine(G)composes the D614G mutation that is around 20%more infectious than its predecessor 614D.The B117 variant,that exhibits a 70%transmissibility rate,harbours 23 mutants,each reflecting one amino acid exchange.We examined several globally spreading mutations,501.V2,B1351,P1,and others,with respect to the specific amino acid conversions involved.Unlike previous versions of coronavirus,where random mutations eventually precipitate extinction,the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious,facilitating its ability to evade detection,thus challenging the effectiveness of a large variety of emerging vaccines.Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein,restricting the virus from releasing its contents into the cell.Developing antibodies during the innate response,appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I,compromising adaptive efficiency to recognize the virus,possibly provoking a cytokine storm that injures vital organs.With respect to that perspective,the potential safety and effectiveness of different vaccines are evaluated and compared,including the Spike protein mRNA version,the Adenovirus DNA,Spike protein subunits,the deactivated virus genres,or,finally,the live attenuated coronavirus that appears to demonstrate the greatest effectiveness,yet,encompass a relatively higher risk.
基金This work was supported by the Beijing Natural Science Foundation(M23008)the National Key Research and Development Program of China(2018YFE0207300)+2 种基金Beijing Municipal Science&Technology Commission(Z211100002521021)the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-124)Key Research and Development Plan of Hebei Province,Special Health Innovation Project(22377744D).
文摘Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
基金supported by the National Science and Technology Major Project of China(No.2017ZX10202203-007,No.2017ZX10202203-008,and No.2018ZX10302206-003)a pilot project of clinical cooperation between traditional Chinese and western medicine for significant and complicated diseases of National Administration of Traditional Chinese Medicine:hepatic fibrosis.We also acknowledge the support of the National Natural Science Foundation of China(No.81772198)+1 种基金the Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-msxmX0389)General Project of Chongqing Natural Science Foundation(No.cstc2020jcyj-msxmX0015).
文摘Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.
基金This study was supported by the National Major Science and Technology Project of China(2018ZX10711001 and 2013ZX09102029)The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines and therapeutics against SFTSV currently.B‐Propiolactone(BPL)inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 adjuvant.The experimental SFTS vaccine was a satisfying immunogen,which could efficiently trigger the development of high levels of SFTSV NP‐specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice,and could induce SFTS virus‐specific cellular immune responses to a certain extent.A single dose of vaccine was immunogenically insufficient in BALB/c mice;the second and third dose resulted in significant boost in antibody response.The use of Al(OH)3 adjuvant resulted in higher antibody titers.The mediate‐dose of vaccine could induce as high and equivalent level of antibody titer as that of high‐dose.The experimental SFTS vaccine in mediate‐and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild‐type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with controls.The experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice,and could protect C57/BL6 mice against SFTS virus challenge.These results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.
文摘Mucosal vaccination,which has the potential to induce both mucosal and systemic immune responses,is considered the most suitable method of preventing infectious diseases in farmed fish.Aeromonas veronii and Edwardsiella ictaluri are two pathogenic bacteria found in yellow catfish and often infect the fish through mucosal surfaces.Delivery of a bivalent inactivated vaccine by injection has been shown to induce a strong systemic immune response against both bacterial infections.However,mucosal immune responses and protective efficiency induced by this inactivated vaccine administrated via immersion are yet to be investigated.We developed a bivalent vaccine containing formalin-inactivated A.veronii and E.ictaluri and evaluated the immune response in yellow catfish after immersion vaccination using body fluids biochemistry indices,agglutinating antibody titers,and the expression level of immune-related genes in the skin,gills,spleen,and head kidney.The activities of innate immune-related enzymes and specific agglutination antibody titers in body fluids,as well as the expression of innate and adaptive immune-related genes in both the mucosal and systemic tissues of vaccinated fish,were significantly higher than that in control fish.Next,we assessed the protective efficacy by a challenge model of virulent strains of E.ictaluri and A.veronii.The relative survival percent of vaccinated fish was 80%and 87%after challenging fish with E.ictaluri and A.veronii,respectively,which was higher than unvaccinated control fish(43%and 57%).These results confirm that the bivalent inactivated vaccine administered via immersion induces a strong mucosal immune response and confers good protection against both E.ictaluri and A.veronii.Our results also reinforce the notion that immersion vaccination could stimulate both mucosal and systemic immunity contributing to protection against pathogens.
基金Guangzhou Health Science and Technology Project(20201A011078)Guangzhou Science and Technology Project(202102010094)+5 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515012550)Clinical research project of Guangzhou Medical University Second Affiliated Hospital(2021-LCYJ-05)Guangdong Medical Research Fund(A2022255)Key Clinical Specialty of Guangzhou Medical University(0F03031)Guangzhou Laboratory(EKPG21-30-3)Guangzhou key discipline of urology.The funding sources had no role in the study design,data collection,analysis,interpretation,or writing of the report.
文摘Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.
基金The study was supported by the COVID-19 Project of Shanxi Provincial Finance, and the Project of Shanxi Provincial Key Laboratory for major infectious disease response.
文摘Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population.Methods: In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis.Results: A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0-14, 0-21, and 0-28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95%CI: 88.4-108.4) in the 0-14 group, which was significantly lower compared with 134.4 (95%CI: 123.1-145.7) in the 0-21 group (P < 0.001 vs 0-14 group) and 145.5 (95%CI: 131.3-159.6) in the 0-28 group (P < 0.001 vs 0-14 group), resulting in the seroconversion rates to neutralizing antibodies (GMT ≥ 16) of 100.0% for all three groups, respectively. The intention-to-treat (ITT) analysis yielded similar results. All reported adverse reactions were mild.Conclusions: Both a two-dose of inactivated SARS-CoV-2 vaccine at 0-21 days and 0-28 days regimens significantly improved SARS-CoV-2 neutralizing antibody level compared to the 0-14 days regimen in high-risk occupational population, with seroconversion rates of 100.0%.
基金supported by the Emergency Key Program of Guangzhou Laboratory(No.EKPG21-30)the Fundamental Research Funds for the Central Universities(No.2019kfyXMBZ015)+1 种基金the Fellowship of China Postdoctoral Science Foundation(Nos.2020T130034ZX and 2020M680102)the National Natural Science Foundation of China(Nos.72061137006 and 82204113).
文摘Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response.To this end,a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted,and the participants were followed up at 3.3(Visit 1),9.2(Visit 2),and 18.5(Visit 3)months after SARS-CoV-2 infection.They were classified into three groups(no-vaccination(n=54),one-dose(n=62),and two-dose(n=92)groups)on the basis of the administration of inactivated vaccination.The neutralizing antibody(NAb)titers against the wild-type virus continued to decrease in the no-vaccination group,but they rose significantly in the one-dose and two-dose groups,with the highest NAb titers being observed in the two-dose group at Visit 3.The NAb titers against the Delta variant for the no-vaccination,one-dose,and two-dose groups decreased by 3.3,1.9,and 2.3 folds relative to the wild-type virus,respectively,and those against the Omicron variant decreased by 7.0,4.0,and 3.8 folds,respectively.Similarly,the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose.Results showed that the convalescents benefited from the administration of the inactivated vaccine(one or two doses),which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses.Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic,and vaccination guidelines and policies need to be updated.
基金sponsored by the National Natural Science Foundation of China(81672018)the National 13th Five-Year Grand Program on Key Infectious Disease Control(2017ZX10202102)+2 种基金the 13th Five-Year National Science and Technology Major Project for infectious Diseases(2017ZX10305501-002)Shanghai Pujiang Program(19PJ1409100)the Technology Service Platform for Detecting High level Biological Safety Pathogenic Microorganism Supported by Shanghai Science and Technology Commission(18DZ2293000)。
文摘Hand,foot,and mouth disease(HFMD)recently emerged as a global public threat.The licensure of inactivated enterovirus A71(EV-A71)vaccine was the first step in using a vaccine to control HFMD.New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage.The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines.The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes.The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response.
基金the National Key Research and Development Program of China(No.2022YFD1800100).
文摘Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines.In this study,we constructed a recombinant virus,rCVS11-LTB,which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit(LTB)protein on the surface of the RABV particles.Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells(DCs).Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virusneutralizing antibodies(VNAs)in both mice and dogs than the parent virus rCVS11,to enhance the cellular immune response and T cell immune memory in mice,and was also able to provide 100%protection in mice from lethal doses of rabies virus,indicating its potential as a safe and effective inactivated rabies vaccine candidate.
基金This work was supported by the Bill&Melinda Gates Foundation(Grant No.INV-049539)the Key Research and Development Program of Hainan Province(Grant No.ZDYF2020210)+1 种基金the Project of the National Social Science Fund of China(Grant No.20BGL264)the Shanghai Public Health System Construction Three-Year Action Plan(Grant No.GWVI-11.1-48)。
文摘Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomic status,cultural beliefs,concerns about vaccine safety,and cost may hinder caregivers from vaccinating their children.Further measures,such as health education campaigns to raise knowledge and awareness,and encouragement of domestic vaccine innovation,which would reduce out-of-pocket costs,could be implemented to improve the coverage of DTap-IPV/Hib vaccination.
