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

• DOI: 10.1038/s41385-022-00511-0
• Publication Date: 2022-04-25T17:03:53Z
• Authors: Salma Sheikh-Mohamed; Baweleta Isho; Gary Y.C. Chao; Michelle Zuo; Carmit Cohen; Yaniv Lustig; George R. Nahass; Rachel E. Salomon...; Grace Blacker; Mahya Fazel-Zarandi; Bhavisha Rathod; Karen Colwill; Alainna Jamal; Zhijie Li; Keelia Quinn de L...; Alyson Takaoka; Julia Garnham-Tak...; Anjali Patel; Christine Fahim; Aimee Paterson; Angel Xinliu Li; Nazrana Haq; Shiva Barati; Lois Gilbert; Karen Green; Mohammad Mozafari...; Philip Samaan; Patrick Budylowski; Walter L. Siqueira; Samira Mubareka; Mario Ostrowski; James M. Rini; Olga L. Rojas; Irving L. Weissman; Michal Caspi Tal; Allison McGeer; Gili Regev-Yochay; Sharon Straus; Anne-Claude Gingras; Jennifer L. Gomme...
• Keywords: COVID-19 Vaccines; SARS-CoV-2; Brief-Communication; Vaccination; COVID-19; Humans; Viral Vaccines; Prospective Studies; RNA, Messenger; Antibodies, Viral; 16. Peace & justice; Secretory Component; 3. Good health

AbstractAlthough SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated at this site in response to intramuscular COVID-19 vaccination, and whether these Ab protect against subsequent “breakthrough” infections. We collected longitudinal serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines over a 6-month period and measured the relative level of anti-Spike and anti-Receptor Binding Domain (RBD) Ab. We detected anti-Spike/RBD IgG and IgA and associated secretory component in the saliva of most participants receiving 1 dose of mRNA vaccine. 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 greatly diminished anti-Spike/RBD IgG and IgA levels concomitant with a reduction in neutralizing activity in the saliva, although the level of secretory component associated anti-Spike was less susceptible to decay. Examining two prospective cohorts of subjects that were monitored for infections post-vaccination, we found that participants who were subsequently infected with SARS-CoV-2 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 emphasize the importance of developing COVID-19 vaccines that elicit a durable IgA response.One-Sentence SummaryOur study delves into whether intra-muscular mRNA vaccination regimes confer a local IgA response in the oral cavity and whether the IgA response is associated with protection against breakthrough infection.