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Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection

Salma Sheikh‐MohamedDepartment of Immunology, University of Toronto, Toronto, ON, CanadaBaweleta IshoDepartment of Immunology, University of Toronto, Toronto, ON, CanadaGary ChaoDepartment of Immunology, University of Toronto, Toronto, ON, CanadaMichelle ZuoDepartment of Immunology, University of Toronto, Toronto, ON, CanadaCarmit CohenSheba Medical Center Tel Hashomer, Ramat Gan, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, IsraelYaniv LustigCentral Virology Laboratory, Public Health Services, Ministry of Health, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Tel Aviv-Yafo, IsraelGeorge R. NahassInstitute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA, USARachel E. Salomon-ShulmanInstitute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA, USAGrace BlackerInstitute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA, USAMahya Fazel‐ZarandiLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaBhavisha RathodLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaKaren ColwillLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaAlainna JamalLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaZhijie LiDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaKeelia Quinn de LaunayLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, CanadaAlyson TakaokaLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, CanadaJulia Garnham-TakaokaLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, CanadaAnjali PatelLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, CanadaChristine FahimLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, CanadaAimee PatersonLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaAngel Xinliu LiLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaNazrana HaqLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaShiva BaratiLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaLois GilbertLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaKaren GreenLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaMohammad MozafarihashjinLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaPhilip SamaanDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaPatrick BudylowskiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaWalter L. SiqueiraCollege of Dentistry, University of Saskatchewan, Saskatoon, SK, CanadaSamira MubarekaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaMario OstrowskiDepartment of Immunology, University of Toronto, Toronto, ON, CanadaJames M. RiniDepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaOlga L. RojasKrembil Research Institute, University Health Network, Toronto, ON, CanadaIrving L. WeissmanInstitute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA, USAMichal Caspi TalInstitute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, CA, USAAllison McGeerLunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, CanadaGili Regev‐YochaySheba Medical Center Tel Hashomer, Ramat Gan, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, IsraelSharon E. StrausLi Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. [email protected]Anne‐Claude GingrasDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada. [email protected]Jennifer L. GommermanDepartment of Immunology, University of Toronto, Toronto, ON, Canada. [email protected]
2022en
ABI

Аннотация

Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.

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