Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination
Authors: Gorochov Guy , Ropers Jacques , Launay Odile , Dorgham Karim , da Mata-Jardin Omaira , Lebbah Said , Durier Christine , Bauer Rebecca , Radenne Anne , Desaint Corinne , Vieillard Louis-Victorien , Rekacewicz Claire , Lachatre Marie , Parfait Béatrice , Batteux Frédéric , Hupé Philippe , Ninove Läétitia , Lefebvre Maeva , Conrad Anne , Dussol Bertrand , Maakaroun-Vermesse Zoha , Melica Giovanna , Nicolas Jean-François , Verdon Renaud , Kiladjian Jean-Jacques , Loubet Paul , Schmidt-Mutter Catherine , Dualé Christian , Ansart Séverine , Botelho-Nevers Elisabeth , Lelièvre Jean-Daniel , de Lamballerie Xavier , Kieny Marie-Paule , Tartour Eric , Paul Stéphane 
Published: April 2024

Importance

There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response.

Objective

To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection.

Design, Setting, and Participants

In this cohort study, SARS-CoV-2–naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023.

Main Outcomes and Measures

An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times.

Results

A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2–naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2–naive individuals. After vaccination, SARS-CoV-2–specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10−5 vs 37 × 10−5 at day 29; 107 × 10−5 vs 54 × 10−5 at day 57; and 104 × 10−5 vs 70 × 10−5 at day 180 [P &amp;lt; .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2–naive group increased only at day 57 (36 × 10−5 vs 49 × 10−5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2–naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P &amp;lt; .001).

Conclusions and Relevance

The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.