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. 2024 Apr 1;7(4):e248051.
doi: 10.1001/jamanetworkopen.2024.8051.

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

Guy Gorochov  1 , Jacques Ropers  2 , Odile Launay  3 , Karim Dorgham  1 , Omaira da Mata-Jardin  1 , Said Lebbah  2 , Christine Durier  4 , Rebecca Bauer  4 , Anne Radenne  5 , Corinne Desaint  3 , Louis-Victorien Vieillard  3 , Claire Rekacewicz  3 , Marie Lachatre  3 , Béatrice Parfait  6 , Frédéric Batteux  7 , Philippe Hupé  8   9 , Läétitia Ninove  10 , Maeva Lefebvre  11 , Anne Conrad  12 , Bertrand Dussol  13 , Zoha Maakaroun-Vermesse  14 , Giovanna Melica  15 , Jean-François Nicolas  16 , Renaud Verdon  17 , Jean-Jacques Kiladjian  18 , Paul Loubet  19 , Catherine Schmidt-Mutter  20 , Christian Dualé  21 , Séverine Ansart  22 , Elisabeth Botelho-Nevers  23 , Jean-Daniel Lelièvre  24 , Xavier de Lamballerie  10 , Marie-Paule Kieny  25 , Eric Tartour  26 , Stéphane Paul  27
Affiliations

Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination

Guy Gorochov et al. JAMA Netw Open. .

Abstract

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 < .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 < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Launay reported receiving nonfinancial support from Pfizer Inc, MSD, Sanofi SA, and AstraZeneca, grant funding from Moderna Inc, Pfizer Inc, MSD, Sanofi SA, and AstraZeneca, and personal fees from Moderna Inc, Pfizer Inc, MSD, Sanofi SA, and AstraZeneca outside the submitted work. Dr Conrad reported consulting for Pfizer Inc and Moderna Inc outside the submitted work. Dr Schmidt-Mutter reported receiving financial support for personal and material investigation from Assistance Publique–Hôpitaux de Paris (AP-HP) outside the submitted work. Dr Dualé reported receiving grant funding from INSERM during the conduct of the study. Dr Botelho-Nevers reported participating on the scientific advisory boards for Pfizer Inc, Moderna Inc, Sanofi SA, and Janssen Global Services LLC outside the submitted work. Dr de Lamballerie reported receiving grant funding from the French Ministry of Research during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Longitudinal Evolution of Serum and Salivary Anti–Spike IgG and IgA Following Messenger RNA (mRNA) Vaccination in Individuals With or Without Previous Exposure to SARS-CoV-2
Evolution over time in individuals with previous SARS-CoV-2 infection receiving the BNT162b2 (Pfizer-BioNTech) vaccine, SARS-CoV-2–naive individuals receiving the mRNA-1273 (Moderna) vaccine, and SARS-CoV-2–naive individuals receiving BNT162b2 (Pfizer-BioNTech) of median log10 levels of salivary and serum anti–spike IgG or IgA at days 1, 29, 57, and 180 after vaccination. Error bars indicate 95% CI. Dotted lines indicate threshold values computed as mean plus 1 SD of measurements made at day 1 among patients without prior infection. Results of comparison between groups at each time (Wilcoxon rank sum test) are shown. aP ≤ .001, previous infection vs infection naive with mRNA-1273 vaccine. bP ≤ .001, previous infection vs infection naive with BNT162b2 vaccine. cP ≤ .001, infection naive with mRNA-1273 vaccine vs infection naive with BNT162b2 vaccine.
Figure 2.
Figure 2.. Salivary Anti–Spike IgG Response Following Messenger RNA (mRNA) Vaccination
Evolution over time in SARS-CoV-2–naive individuals receiving the mRNA-1273 (Moderna) vaccine or BNT162b2 (Pfizer-BioNTech) vaccine and previously infected individuals receiving BNT162b2 (Pfizer-BioNTech) of median log10 salivary anti–spike IgG normalized on total salivary IgG levels at days 1, 29, 57, and 180 after vaccination, measured using digital enzyme-linked immunosorbent assay. Dotted lines indicate threshold values computed as mean plus 1 SD of measurements made at day 1 among patients without prior infection. Horizontal blue bars indicate median values. Results of the comparison between time points (Wilcoxon rank sum test) are provided in eTable 5 in Supplement 1.
Figure 3.
Figure 3.. Salivary Anti–Spike IgA Response Following Messenger RNA (mRNA) Vaccination
Evolution over time in SARS-CoV-2–naive individuals receiving the mRNA-1273 (Moderna) vaccine or the BNT162b2 (Pfizer-BioNTech) vaccine and previously infected individuals receiving BNT162b2 (Pfizer-BioNTech) of median log10 salivary anti–spike IgA levels normalized on total salivary IgA at days 1, 29, 57, and 180 after vaccination, measured using digital enzyme-linked immunosorbent assay (taking into account both monomeric and multimeric secretory IgA). Dotted lines indicate threshold values computed as mean plus 1 SD of measurements made at day 1 among patients without prior infection. Horizontal blue bars indicate median values. Results of the comparison between time points (Wilcoxon rank sum test) are provided in eTable 5 in Supplement 1.
Figure 4.
Figure 4.. Multimeric Secretory Anti–Spike IgA After Vaccination in the Saliva of Individuals With Previous Infection Compared With SARS-CoV-2–Naive Individuals
Measure of anti–spike secretory IgA by classic enzyme-linked immunosorbent assay, using antisecretory piece detection antibodies. SARS-CoV-2–naive individuals received the mRNA-1273 (Moderna) vaccine and previously infected individuals received the BNT162b2 (Pfizer-BioNTech) vaccine. Horizontal orange bars indicate median values. Results of the comparison between groups (Wilcoxon rank sum test) are shown. aP ≤ .01, days 1 vs 57, for infection-naive participants receiving mRNA-1273 vaccine. bP ≤ .001, day 57 for infection-naive participants receiving mRNA-1273 vaccine vs day 29 for previously infected individuals.
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References

    1. Brandtzaeg P. Induction of secretory immunity and memory at mucosal surfaces. Vaccine. 2007;25(30):5467-5484. doi:10.1016/j.vaccine.2006.12.001 - DOI - PubMed
    1. Sterlin D, Mathian A, Miyara M, et al. . IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med. 2021;13(577):eabd2223. doi:10.1126/scitranslmed.abd2223 - DOI - PMC - PubMed
    1. Havervall S, Marking U, Svensson J, et al. . Anti-spike mucosal IgA protection against SARS-CoV-2 Omicron infection. N Engl J Med. 2022;387(14):1333-1336. doi:10.1056/NEJMc2209651 - DOI - PMC - PubMed
    1. Sheikh-Mohamed S, Isho B, Chao GYC, et al. . Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection. Mucosal Immunol. 2022;15(5):799-808. doi:10.1038/s41385-022-00511-0 - DOI - PMC - PubMed
    1. Sano K, Bhavsar D, Singh G, et al. ; PARIS Study Group . SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals. Nat Commun. 2022;13(1):5135. doi:10.1038/s41467-022-32389-8 - DOI - PMC - PubMed

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