TY - JOUR
T1 - mRNA COVID-19 vaccination induces minimal IgA in saliva in the absence of prior clinical or subclinical infection
AU - Conner, Tonia L.
AU - Goguet, Emilie
AU - Haines-Hull, Hannah
AU - Segard, Allison
AU - Darcey, Emily S.
AU - Kobi, Priscilla
AU - Balogun, Bolatito
AU - Olsen, Cara
AU - Esposito, Dominic
AU - Jones, Milissa U.
AU - Burgess, Timothy H.
AU - O'Connell, Robert J.
AU - Broder, Christopher C.
AU - Saunders, David
AU - Pollett, Simon
AU - Laing, Eric D.
AU - Mitre, Edward
N1 - Publisher Copyright:
Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026/5/22
Y1 - 2026/5/22
N2 - In this prospective cohort study, we analyzed saliva IgA and IgG antibody levels over the first two years of the pandemic after COVID-19 mRNA vaccination and infection. Generally healthy adult healthcare workers with no evidence of prior SARS-CoV-2 infection were enrolled into the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study between August of 2020 and March of 2021. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, and secretory IgA in 1224 saliva samples collected from 266 individuals between August of 2020 through December of 2022. By the summer of 2022, 45.2% of the cohort had tested positive for SARS-CoV-2 by antigen or PCR test at least once and another 42.2% had evidence of prior subclinical infection as denoted by a doubling in saliva anti-SARS-CoV-2 nucleocapsid (N) IgG level. While many individuals had elevations in saliva spike-specific antibodies by spring of 2022, analyses revealed that most elevations in saliva spike-specific IgA and secretory IgA were driven by subclinical and clinically evident infections. Removal of saliva samples after positive COVID-19 testing or evidence of subclinical infection revealed that two doses of BNT162b2 induced only minimal (1.6-fold) increases in saliva anti-spike IgA levels at one month after the second vaccination. In contrast, saliva anti-spike IgG was strongly induced by vaccination and exhibited improved durability with hybrid immunity. We also observed that females produced higher levels of saliva anti-spike IgA and IgG antibodies than males in response to mRNA vaccination, that the half-life of anti-spike IgG in saliva after two mRNA vaccine doses is ∼90 days, and that in the setting of hybrid immunity saliva anti-spike IgA levels are greater when infection follows vaccination than when vaccination follows infection. This study demonstrates that intramuscular mRNA vaccines are weak inducers of IgA antibodies in saliva.
AB - In this prospective cohort study, we analyzed saliva IgA and IgG antibody levels over the first two years of the pandemic after COVID-19 mRNA vaccination and infection. Generally healthy adult healthcare workers with no evidence of prior SARS-CoV-2 infection were enrolled into the Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study between August of 2020 and March of 2021. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, and secretory IgA in 1224 saliva samples collected from 266 individuals between August of 2020 through December of 2022. By the summer of 2022, 45.2% of the cohort had tested positive for SARS-CoV-2 by antigen or PCR test at least once and another 42.2% had evidence of prior subclinical infection as denoted by a doubling in saliva anti-SARS-CoV-2 nucleocapsid (N) IgG level. While many individuals had elevations in saliva spike-specific antibodies by spring of 2022, analyses revealed that most elevations in saliva spike-specific IgA and secretory IgA were driven by subclinical and clinically evident infections. Removal of saliva samples after positive COVID-19 testing or evidence of subclinical infection revealed that two doses of BNT162b2 induced only minimal (1.6-fold) increases in saliva anti-spike IgA levels at one month after the second vaccination. In contrast, saliva anti-spike IgG was strongly induced by vaccination and exhibited improved durability with hybrid immunity. We also observed that females produced higher levels of saliva anti-spike IgA and IgG antibodies than males in response to mRNA vaccination, that the half-life of anti-spike IgG in saliva after two mRNA vaccine doses is ∼90 days, and that in the setting of hybrid immunity saliva anti-spike IgA levels are greater when infection follows vaccination than when vaccination follows infection. This study demonstrates that intramuscular mRNA vaccines are weak inducers of IgA antibodies in saliva.
KW - COVID-19 mRNA vaccine
KW - Mucosal immunity
KW - SARS-CoV-2 infection
KW - Saliva antibodies
KW - Secretory IgA (SIgA)
KW - Subclinical infection
UR - https://www.scopus.com/pages/publications/105036688370
U2 - 10.1016/j.vaccine.2026.128612
DO - 10.1016/j.vaccine.2026.128612
M3 - Article
C2 - 42033975
AN - SCOPUS:105036688370
SN - 0264-410X
VL - 82
JO - Vaccine
JF - Vaccine
M1 - 128612
ER -