The upper respiratory tract is the initial site of SARS-CoV-2 infection.Nasal spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough infection.We report that intranasal ...The upper respiratory tract is the initial site of SARS-CoV-2 infection.Nasal spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough infection.We report that intranasal vaccination using human adenovirus serotype 5(Ad5)vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing slgA in the nasal passage.Nasal slgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40%of total proteins in nasal mucosal lining fluids(NMLFs).A low-level IgG could also be detected in NMLFs but not IgM,IgD,and IgE.After a complete nasal wash,slgA in the nasal passage could be replenished rapidly within a few hours.A comparison of purified paired serum IgA,serum IgG,and nasal slgA from the same individuals showed that slgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants.Serum IgG and IgA failed to neutralize XBB and BA.2.86,while nasal slgA retained potent neutralization against these newly emerged variants.Further analysis showed that slgA Was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge.Using a slgA monoclonal antibody as a reference,we estimated that the total nasal slgA contains about 2.6-3.9%spikespecific slgA in NMLFs collected approximately one month after intranasal vaccination.Our study provided insights for developing intranasal vaccines that can induce slgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.展开更多
基金The study was supported by the National Natural Science Foundation(92269201)Youth Innovation Promotion Association of CAS(2022361)+2 种基金Grants from Guangzhou National Laboratory(GZNL2024A01012,GZNL2023A01009)State Key Laboratory of Respiratory Disease(SKLRD-Z-202106,SKLRD-Z-202328)Science and Technology Projects in Guangzhou(SL2022A04J00604).
文摘The upper respiratory tract is the initial site of SARS-CoV-2 infection.Nasal spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough infection.We report that intranasal vaccination using human adenovirus serotype 5(Ad5)vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing slgA in the nasal passage.Nasal slgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40%of total proteins in nasal mucosal lining fluids(NMLFs).A low-level IgG could also be detected in NMLFs but not IgM,IgD,and IgE.After a complete nasal wash,slgA in the nasal passage could be replenished rapidly within a few hours.A comparison of purified paired serum IgA,serum IgG,and nasal slgA from the same individuals showed that slgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants.Serum IgG and IgA failed to neutralize XBB and BA.2.86,while nasal slgA retained potent neutralization against these newly emerged variants.Further analysis showed that slgA Was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge.Using a slgA monoclonal antibody as a reference,we estimated that the total nasal slgA contains about 2.6-3.9%spikespecific slgA in NMLFs collected approximately one month after intranasal vaccination.Our study provided insights for developing intranasal vaccines that can induce slgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.
