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
The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,is essential for stopping the current coronavirus disease(COVID-19)pandemic.A v...The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,is essential for stopping the current coronavirus disease(COVID-19)pandemic.A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection.Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)since the outbreaks of these diseases.The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses.In this review,we present the status of the development of coronavirus vaccines,focusing particularly on the biomimetic nanoparticle technology platform,which is likely to have a major role in future developments of personalized medicine.展开更多
During the last decades,the use of nanotechnology in med icine has effectively been translated to the design of drug delivery systems,nanostructured tissues,diagnostic platforms,and novel nanomaterials against several...During the last decades,the use of nanotechnology in med icine has effectively been translated to the design of drug delivery systems,nanostructured tissues,diagnostic platforms,and novel nanomaterials against several human diseases and infectious pathogens.Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2.To fast-track the development of vaccines,unprecedented industrial and academic collaborations emerged around the world,resulting in the clinical translation of effective vaccines in less than one year.In this article,we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used,their mechanisms of action,obtained results during each phase of their clinical development and their regulatory approval process.We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.展开更多
<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many co...<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>展开更多
Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to ra...Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to rapid mutation,encodes both structural and non-structural proteins.Vaccination is currently the only effective method to prevent COVID-19,and structural proteins are critical targets for vaccine development.Currently,many vaccines are in clinical trials or are already on the market.This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19,including viral vector vaccines,DNA vaccines,RNA vaccines,live-attenuated vaccines,inactivated virus vaccines,recombinant protein vaccines and bionic nanoparticle vaccines.In addition to traditional inactivated virus vaccines,some novel vaccines based on viral vectors,nanoscience and synthetic biology also play important roles in combating COVID-19.However,many challenges persist in ongoing clinical trials.展开更多
BACKGROUND The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has produced a global pandemic of coronavirus disease 2019(COVID-19),resulting in modifications to public health policies on a u...BACKGROUND The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has produced a global pandemic of coronavirus disease 2019(COVID-19),resulting in modifications to public health policies on a universal scale.SARSCoV-2 vaccine has evolved as the most effective and secure way for protecting healthy individuals against COVID-19.Patients with cancer were excluded from clinical trials due to their increased COVID-19 risk and current immunosuppressing therapy.Safety and effectiveness evidence is insufficient for SARS-CoV-2 vaccination in cancer patients.AIM To assess the efficacy and safety of two-dose SARS-CoV-2 vaccines in cancer patients.METHODS A multicenter observational study was performed at ten Chinese hospitals between January 1,2021 and December 31,2021.Each participant in the research received two doses of vaccination.A total of 215 healthy people were screened and 132 eligible patients with cancer were recruited.In order to verify the safety of the second dose of the vaccine,a side-effect report was compiled.Two weeks following the second vaccination dose,subjects underwent an analogous questionnaire survey.Utilizing a magnetic particle-based chemiluminescence immunoassay,serum levels of anti-SARS-CoV-2 immunoglobulin G(IgG)antibodies were measured to determine the effectiveness of vaccination.IgG levels≥10 AU/mL were considered seropositive.RESULTS All the 347 eligible patients completed the follow-up,and anti-SARS-CoV-2 IgG antibodies were detected.Local pain at the injection location was the most common side effect mentioned by all responders,with an increased incidence in cancer patients than the healthy people after the second dose vaccine(17.2%vs 9.1%;P=0.035).There was no significant difference in headache,urticaria,or other adverse reactions between patients with cancer and healthy people.In the group of cancer patients,the seropositivity incidence was 83.3%,while it was 96.3%in the group of healthy people.In the group of cancer patients,the seropositivity incidence and antibody levels were significantly lower(P<0.001).This analysis showed a poorer response rate in patients on active immunosuppressive treatment and elderly cancer patients.CONCLUSION Two-dose Chinese vaccines are effective and safe in cancer patients.However,further research is required on the efficacy in elderly cancer patients and those on active immunosuppressive treatment.展开更多
BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease...BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.展开更多
Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillan...Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.展开更多
Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the produc...Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.展开更多
Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to...Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30<sup>th</sup> to August 30<sup>th</sup>, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.展开更多
In the context of SARS-CoV-2 pandemic,mathematical modelling has played a funda-mental role for making forecasts,simulating scenarios and evaluating the impact of pre-ventive political,social and pharmaceutical measur...In the context of SARS-CoV-2 pandemic,mathematical modelling has played a funda-mental role for making forecasts,simulating scenarios and evaluating the impact of pre-ventive political,social and pharmaceutical measures.Optimal control theory represents a useful mathematical tool to plan the vaccination campaign aimed at eradicating the pandemic as fast as possible.The aim of this work is to explore the optimal prioritisation order for planning vaccination campaigns able to achieve specific goals,as the reduction of the amount of infected,deceased and hospitalized in a given time frame,among age classes.For this purpose,we introduce an age stratified SIR-like epidemic compartmental model settled in an abstract framework for modelling two-doses vaccination campaigns and conceived with the description of COVID19 disease.Compared to other recent works,our model incorporates all stages of the COVID-19 disease,including death or recovery,without accounting for additional specific compartments that would increase computa-tional complexity and that are not relevant for our purposes.Moreover,we introduce an optimal control framework where the model is the state problem while the vaccine doses administered are the control variables.An extensive campaign of numerical tests,featured in the Italian scenario and calibrated on available data from Dipartimento di Protezione Civile Italiana,proves that the presented framework can be a valuable tool to support the planning of vaccination campaigns.Indeed,in each considered scenario,our optimization framework guarantees noticeable improvements in terms of reducing deceased,infected or hospitalized individuals with respect to the baseline vaccination policy.展开更多
Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from...Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.展开更多
Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the...Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.展开更多
目的系统评价糖尿病患者在接种SARS-CoV-2疫苗后的体液和细胞免疫反应。方法检索Web of Science、PubMed、中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库和中国生物医学文献数据库,获取国内外于2019年12月1日至2022年5...目的系统评价糖尿病患者在接种SARS-CoV-2疫苗后的体液和细胞免疫反应。方法检索Web of Science、PubMed、中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库和中国生物医学文献数据库,获取国内外于2019年12月1日至2022年5月12日公开发表的有关糖尿病患者接种SARS-CoV-2疫苗后的体液和细胞免疫反应的观察性研究,经由2名研究者独立筛选文献和提取资料后,采用美国国立卫生研究质量评价工具对纳入文献进行偏倚风险评价,使用描述性统计方法进行汇总分析。结果13篇文献共纳入66651例研究对象,其中5874例(7.9%)患有糖尿病。7篇文献报道了接种第1剂疫苗后糖尿病患者和对照组的免疫反应,其中3篇文献表明,接种1剂SARS-CoV-2疫苗后,糖尿病患者血清抗体水平和阳性率低于对照组;11篇涉及接种2剂SARS-CoV-2疫苗后的免疫反应的文献中,2篇报道了糖尿病患者可产生与对照组相似的抗体反应,9篇报道了糖尿病患者的血清抗体水平、阳性率或细胞免疫反应低于对照组。结论接种SARS-CoV-2疫苗后糖尿病患者和对照组体液和细胞免疫反应均有所增加,但糖尿病患者增加幅度普遍低于对照组。展开更多
Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observat...Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observational medication study on acquired immunity and effectiveness of vaccines. Population: 620 workers in the health service of Almansa (Spain). Representative sample of 150 individuals. Sociodemographic, clinical, and epidemiological data and samples were recorded to determine anti-SARS-CoV-2 serum IgG levels 6 and 9 months after vaccination with Pfizer. Results: Mean age 46.45 years;76% women;85.1% working in a hospital. 19.3% had had COVID-19 in the year prior to vaccination. 96.7% were fully vaccinated with Pfizer/BioNTech. At 6 months, 100% seropositivity and mean IgG levels of 3017.2 AU/ml. Significant variations in IgG levels in individuals with prior COVID-19 infection and smokers. At 9 months, 99.3% remained seropositive;2.8% infected after vaccination. The repeated measures analysis showed a difference in means of 669.0 AU/ml (significant decrease in IgG levels of 28.9%). Conclusion: Antibody levels remained positive 6 and 9 months after vaccination, although IgG levels were found to decay.展开更多
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This work was supported by the Fundamental Research Funds for the Central Universities(No.2042020kf1015)National Natural Science Foundation of China(No.81672114,81702627)the Medical talented youth development project in the Health Commission of Hubei Province(No.WJ2019Q049).
文摘The development of a massively producible vaccine against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,is essential for stopping the current coronavirus disease(COVID-19)pandemic.A vaccine must stimulate effective antibody and T cell responses in vivo to induce long-term protection.Scientific researchers have been developing vaccine candidates for the severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS)since the outbreaks of these diseases.The prevalence of new biotechnologies such as genetic engineering has shed light on the generation of vaccines against novel viruses.In this review,we present the status of the development of coronavirus vaccines,focusing particularly on the biomimetic nanoparticle technology platform,which is likely to have a major role in future developments of personalized medicine.
基金supported by NIH Grants R01DK072381,R37DK039773,and TR-002155.
文摘During the last decades,the use of nanotechnology in med icine has effectively been translated to the design of drug delivery systems,nanostructured tissues,diagnostic platforms,and novel nanomaterials against several human diseases and infectious pathogens.Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2.To fast-track the development of vaccines,unprecedented industrial and academic collaborations emerged around the world,resulting in the clinical translation of effective vaccines in less than one year.In this article,we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used,their mechanisms of action,obtained results during each phase of their clinical development and their regulatory approval process.We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.
文摘<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>
基金supported by the National Natural Science Foundation of China(31900950)。
文摘Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to rapid mutation,encodes both structural and non-structural proteins.Vaccination is currently the only effective method to prevent COVID-19,and structural proteins are critical targets for vaccine development.Currently,many vaccines are in clinical trials or are already on the market.This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19,including viral vector vaccines,DNA vaccines,RNA vaccines,live-attenuated vaccines,inactivated virus vaccines,recombinant protein vaccines and bionic nanoparticle vaccines.In addition to traditional inactivated virus vaccines,some novel vaccines based on viral vectors,nanoscience and synthetic biology also play important roles in combating COVID-19.However,many challenges persist in ongoing clinical trials.
文摘BACKGROUND The new coronavirus severe acute respiratory syndrome coronavirus 2(SARSCoV-2)has produced a global pandemic of coronavirus disease 2019(COVID-19),resulting in modifications to public health policies on a universal scale.SARSCoV-2 vaccine has evolved as the most effective and secure way for protecting healthy individuals against COVID-19.Patients with cancer were excluded from clinical trials due to their increased COVID-19 risk and current immunosuppressing therapy.Safety and effectiveness evidence is insufficient for SARS-CoV-2 vaccination in cancer patients.AIM To assess the efficacy and safety of two-dose SARS-CoV-2 vaccines in cancer patients.METHODS A multicenter observational study was performed at ten Chinese hospitals between January 1,2021 and December 31,2021.Each participant in the research received two doses of vaccination.A total of 215 healthy people were screened and 132 eligible patients with cancer were recruited.In order to verify the safety of the second dose of the vaccine,a side-effect report was compiled.Two weeks following the second vaccination dose,subjects underwent an analogous questionnaire survey.Utilizing a magnetic particle-based chemiluminescence immunoassay,serum levels of anti-SARS-CoV-2 immunoglobulin G(IgG)antibodies were measured to determine the effectiveness of vaccination.IgG levels≥10 AU/mL were considered seropositive.RESULTS All the 347 eligible patients completed the follow-up,and anti-SARS-CoV-2 IgG antibodies were detected.Local pain at the injection location was the most common side effect mentioned by all responders,with an increased incidence in cancer patients than the healthy people after the second dose vaccine(17.2%vs 9.1%;P=0.035).There was no significant difference in headache,urticaria,or other adverse reactions between patients with cancer and healthy people.In the group of cancer patients,the seropositivity incidence was 83.3%,while it was 96.3%in the group of healthy people.In the group of cancer patients,the seropositivity incidence and antibody levels were significantly lower(P<0.001).This analysis showed a poorer response rate in patients on active immunosuppressive treatment and elderly cancer patients.CONCLUSION Two-dose Chinese vaccines are effective and safe in cancer patients.However,further research is required on the efficacy in elderly cancer patients and those on active immunosuppressive treatment.
文摘BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.
文摘Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.
文摘Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
文摘Introduction: Following the COVID-19 pandemic, vaccination has been proposed in several countries as the main preventive measure despite very limited data, particularly in dialysis patients. We conducted this study to assess the immunological response to vaccination in Senegalese hemodialysis patients. Patients and Methods: We conducted a prospective study, in two dialysis centers in Dakar from March 30<sup>th</sup> to August 30<sup>th</sup>, 2021 including patients on hemodialysis for >6 months, vaccinated against SARS-CoV-2 according to the vaccination schedule recommended by WHO. A vaccine response was considered positive when seroconversion was observed after one dose of vaccine. The clinical efficacy of immunization was defined as the absence of new COVID-19 infection in patients who received a complete vaccination. Results: Among the 81 patients included in the study, 7.4% had anti-Spike IgM antibodies before their first vaccination. Seroprevalence of IgM antibodies was 38.3% one month after the first vaccine dose (at M1) and 8.6% one month after the second dose (at M4). Anti-Spike IgG antibodies were present in 40.3% of patients before vaccination, in 90.1% at M1, and in 59.7% at M4. Among patients previously infected with SARS-CoV-2, 10.2% had IgM antibodies at M0, 31.6% at M1, and 10.5% at M4 post-vaccination. Similarly, seroprevalences of IgG antibodies in this subgroup were 31.5%, 61.3%, and 50.0% respectively at M0, M1, and M4 post-vaccination. A comparison of seroconversion rates between M0 and M4 showed significant differences only for IgG in COVID-19 naive patients. Mean duration in dialysis and the existence of previous COVID-19 infection were associated with patients’ vaccinal response after the two doses. Age, gender and the use of immunosuppressive treatment did not influence post-vaccinal antibody production. Conclusion: Vaccination against COVID-19 in Senegalese hemodialysis patients induced a low seroconversion rate but it was well tolerated. Moreover, the induced protection was neither strong nor durable, particularly in patients with longer duration in dialysis.
文摘In the context of SARS-CoV-2 pandemic,mathematical modelling has played a funda-mental role for making forecasts,simulating scenarios and evaluating the impact of pre-ventive political,social and pharmaceutical measures.Optimal control theory represents a useful mathematical tool to plan the vaccination campaign aimed at eradicating the pandemic as fast as possible.The aim of this work is to explore the optimal prioritisation order for planning vaccination campaigns able to achieve specific goals,as the reduction of the amount of infected,deceased and hospitalized in a given time frame,among age classes.For this purpose,we introduce an age stratified SIR-like epidemic compartmental model settled in an abstract framework for modelling two-doses vaccination campaigns and conceived with the description of COVID19 disease.Compared to other recent works,our model incorporates all stages of the COVID-19 disease,including death or recovery,without accounting for additional specific compartments that would increase computa-tional complexity and that are not relevant for our purposes.Moreover,we introduce an optimal control framework where the model is the state problem while the vaccine doses administered are the control variables.An extensive campaign of numerical tests,featured in the Italian scenario and calibrated on available data from Dipartimento di Protezione Civile Italiana,proves that the presented framework can be a valuable tool to support the planning of vaccination campaigns.Indeed,in each considered scenario,our optimization framework guarantees noticeable improvements in terms of reducing deceased,infected or hospitalized individuals with respect to the baseline vaccination policy.
基金funded by the Emergency prevention and cure Program of COVID-19[22ZXGBSY00010]Tianjin Medical Key Discipline Project[TJYXZDXK-50A]sponsored by Tianjin Municipal Science and Technology Bureau and Tianjin Municipal Health Commission,respectively.
文摘Objective To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.Methods Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age,gender,and vaccination profile.Live virus-neutralizing antibodies against five SARS-CoV-2 variants,including WT,Gamma,Beta,Delta,and Omicron BA.1,and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.Results The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection,but mainly increased the antibody level against the WT strain,and the antibody against the Omicron strain was the lowest.The neutralizing antibody level decreased rapidly 6 months after infection.The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.Conclusion Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1.Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza.Thus,T-lymphocytes may play an important role in recovery.
文摘Objective:Since the opportunity of widespread administration of the fourth mRNA-based coronavirus disease 2019(COVID-19)vaccine dose remains controversial,this article provides a pooled analysis of the efficacy of the second COVID-19 mRNA-based homologous vaccine booster in eliciting anti-SARS-CoV-2 serum antibody response in general immunocompetent populations.Methods:We conducted a digital search in Medline using the keywords"fourth dose"or"second booster"and"antibodies"and"COVID-19"or"SARS-CoV-2"and"BNT162b2"or"mRNA-1273",to identify all clinical studies which evaluated the anti-SARS-CoV-2 serum antibody response after the fourth mRNA-based COVID-19 homologous vaccine dose administration in general immunocompetent populations compared to the response seen before its administration and after the first booster.Results:Four studies totaling 571 recipients of the second mRNA-based COVID-19 vaccine booster were finally included in our analysis.The weighted mean difference(WMD)ratio of anti-SARS-CoV-2 serum antibodies levels measured after and before administration of the fourth vaccine dose was 9.7(95%CI,6.5-12.9)in those receiving BNT162b2 and 12.0(95%CI,5.8-18.2)in those receiving mRNA-1273,respectively.The WMD ratio of anti-SARS-CoV-2 serum antibodies levels measured at the peak of the fourth and third vaccine doses was 1.4(95%CI,1.2-1.7)in those receiving BNT162b2 and 1.9(95%CI,1.5-2.4)in those receiving mRNA-1273,respectively.Conclusion:Our data confirm the efficacy of the fourth mRNA-based COVID-19 vaccine dose in restoring a satisfactory level of anti-SARS-CoV-2 serum antibodies,though such effectiveness seems only marginally superior to that of the first booster.
文摘目的系统评价糖尿病患者在接种SARS-CoV-2疫苗后的体液和细胞免疫反应。方法检索Web of Science、PubMed、中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库和中国生物医学文献数据库,获取国内外于2019年12月1日至2022年5月12日公开发表的有关糖尿病患者接种SARS-CoV-2疫苗后的体液和细胞免疫反应的观察性研究,经由2名研究者独立筛选文献和提取资料后,采用美国国立卫生研究质量评价工具对纳入文献进行偏倚风险评价,使用描述性统计方法进行汇总分析。结果13篇文献共纳入66651例研究对象,其中5874例(7.9%)患有糖尿病。7篇文献报道了接种第1剂疫苗后糖尿病患者和对照组的免疫反应,其中3篇文献表明,接种1剂SARS-CoV-2疫苗后,糖尿病患者血清抗体水平和阳性率低于对照组;11篇涉及接种2剂SARS-CoV-2疫苗后的免疫反应的文献中,2篇报道了糖尿病患者可产生与对照组相似的抗体反应,9篇报道了糖尿病患者的血清抗体水平、阳性率或细胞免疫反应低于对照组。结论接种SARS-CoV-2疫苗后糖尿病患者和对照组体液和细胞免疫反应均有所增加,但糖尿病患者增加幅度普遍低于对照组。
文摘Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observational medication study on acquired immunity and effectiveness of vaccines. Population: 620 workers in the health service of Almansa (Spain). Representative sample of 150 individuals. Sociodemographic, clinical, and epidemiological data and samples were recorded to determine anti-SARS-CoV-2 serum IgG levels 6 and 9 months after vaccination with Pfizer. Results: Mean age 46.45 years;76% women;85.1% working in a hospital. 19.3% had had COVID-19 in the year prior to vaccination. 96.7% were fully vaccinated with Pfizer/BioNTech. At 6 months, 100% seropositivity and mean IgG levels of 3017.2 AU/ml. Significant variations in IgG levels in individuals with prior COVID-19 infection and smokers. At 9 months, 99.3% remained seropositive;2.8% infected after vaccination. The repeated measures analysis showed a difference in means of 669.0 AU/ml (significant decrease in IgG levels of 28.9%). Conclusion: Antibody levels remained positive 6 and 9 months after vaccination, although IgG levels were found to decay.
