Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination
Guy Gorochov
(1, 2)
,
Jacques Ropers
(2, 3)
,
Odile Launay
(4, 5)
,
Karim Dorgham
(1, 2)
,
Omaira da Mata-Jardin
(1, 2)
,
Said Lebbah
(2, 3)
,
Christine Durier
(6)
,
Rebecca Bauer
(6)
,
Anne Radenne
(2)
,
Corinne Desaint
(4, 5)
,
Louis-Victorien Vieillard
(4, 5)
,
Claire Rekacewicz
(4, 5)
,
Marie Lachatre
(4, 5)
,
Béatrice Parfait
(5, 7)
,
Frédéric Batteux
(8, 9)
,
Philippe Hupé
(10, 11)
,
Läétitia Ninove
(12, 13)
,
Maeva Lefebvre
(14, 15)
,
Anne Conrad
(16, 17)
,
Bertrand Dussol
(18, 19)
,
Zoha Maakaroun-Vermesse
(20, 21)
,
Giovanna Melica
(22, 23)
,
Jean-François Nicolas
(16, 24)
,
Renaud Verdon
(25, 26)
,
Jean-Jacques Kiladjian
(27, 28)
,
Paul Loubet
(29, 30)
,
Catherine Schmidt-Mutter
(31, 32)
,
Christian Dualé
(33, 34)
,
Séverine Ansart
(35, 36)
,
Elisabeth Botelho-Nevers
(37, 38)
,
Jean-Daniel Lelièvre
(39, 40)
,
Xavier de Lamballerie
(12, 13)
,
Marie-Paule Kieny
(41)
,
Eric Tartour
(42, 43)
,
Stéphane Paul
(16, 37)
1
CIMI -
Centre d'Immunologie et des Maladies Infectieuses
2 CHU Pitié-Salpêtrière [AP-HP]
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 CIC 1417 - CIC Cochin Pasteur
5 Hôpital Cochin [AP-HP]
6 INSERM SC10 – US19 - INSERM SC10 – US19 Essais thérapeutiques et maladies infectieuses
7 UPCité - Université Paris Cité
8 IC UM3 (UMR 8104 / U1016) - Institut Cochin
9 Servie d'immunologie biologique [CHU Cochin]
10 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
11 Biologie Cellulaire et Cancer
12 UVE - Unité des Virus Emergents
13 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
14 CIC Nantes - Centre d’Investigation Clinique de Nantes
15 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
16 CIRI - Centre International de Recherche en Infectiologie
17 Hôpital de la Croix-Rousse [CHU - HCL]
18 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
19 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
20 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
21 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
22 Hôpital Henri Mondor
23 CIC Henri Mondor - Centre d'Investigation Clinique Henri Mondor
24 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
25 CHU Caen
26 DYNAMICURE - Dynamique Microbienne associée aux Infections Urinaires et Respiratoires
27 AP-HP - Hopital Saint-Louis [AP-HP]
28 CIC-1427 - CIC Saint Louis
29 VBIC - Virulence Bactérienne et Infections Chroniques
30 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
31 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
32 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
33 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
34 CHU Clermont-Ferrand
35 CIC Brest
36 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
37 CIC-EC 1408 - Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne]
38 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
39 IMRB - Institut Mondor de Recherche Biomédicale
40 VRI - Vaccine Research Institute [Créteil, France]
41 INSERM - Institut National de la Santé et de la Recherche Médicale
42 HEGP - Hôpital Européen Georges Pompidou [APHP]
43 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
2 CHU Pitié-Salpêtrière [AP-HP]
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 CIC 1417 - CIC Cochin Pasteur
5 Hôpital Cochin [AP-HP]
6 INSERM SC10 – US19 - INSERM SC10 – US19 Essais thérapeutiques et maladies infectieuses
7 UPCité - Université Paris Cité
8 IC UM3 (UMR 8104 / U1016) - Institut Cochin
9 Servie d'immunologie biologique [CHU Cochin]
10 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
11 Biologie Cellulaire et Cancer
12 UVE - Unité des Virus Emergents
13 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
14 CIC Nantes - Centre d’Investigation Clinique de Nantes
15 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
16 CIRI - Centre International de Recherche en Infectiologie
17 Hôpital de la Croix-Rousse [CHU - HCL]
18 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
19 CIC - Centre d'Investigation Clinique [Hôpital de la Conception - APHM]
20 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
21 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
22 Hôpital Henri Mondor
23 CIC Henri Mondor - Centre d'Investigation Clinique Henri Mondor
24 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
25 CHU Caen
26 DYNAMICURE - Dynamique Microbienne associée aux Infections Urinaires et Respiratoires
27 AP-HP - Hopital Saint-Louis [AP-HP]
28 CIC-1427 - CIC Saint Louis
29 VBIC - Virulence Bactérienne et Infections Chroniques
30 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
31 Centre d’Investigation Clinique Plurithématique (CIC - P) - CIC Strasbourg
32 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
33 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
34 CHU Clermont-Ferrand
35 CIC Brest
36 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
37 CIC-EC 1408 - Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne]
38 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
39 IMRB - Institut Mondor de Recherche Biomédicale
40 VRI - Vaccine Research Institute [Créteil, France]
41 INSERM - Institut National de la Santé et de la Recherche Médicale
42 HEGP - Hôpital Européen Georges Pompidou [APHP]
43 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
Résumé
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.