Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in saliva

Abstract

Vaccines are critical for curtailing the COVID-19 pandemic (1, 2). In the USA, two highly protective mRNA vaccines are available: BNT162b2 from Pfizer/BioNTech and mRNA-1273 from Moderna (3, 4). These vaccines induce antibodies to the SARS-CoV-2 S-protein, including neutralizing antibodies (NAbs) predominantly directed against the Receptor Binding Domain (RBD) (1-4). Serum NAbs are induced at modest levels within ~1 week of the first dose, but their titers are strongly boosted by a second dose at 3 (BNT162b2) or 4 weeks (mRNA-1273) (3, 4). SARS-CoV-2 is most commonly transmitted nasally or orally and infects cells in the mucosae of the respiratory and to some extent also the gastrointestinal tract (5). Although serum NAbs may be a correlate of protection against COVID-19, mucosal antibodies might directly prevent or limit virus acquisition by the nasal, oral and conjunctival routes (5). Whether the mRNA vaccines induce mucosal immunity has not been studied. Here, we report that antibodies to the S-protein and its RBD are present in saliva samples from mRNA-vaccinated healthcare workers (HCW). Within 1-2 weeks after their second dose, 37/37 and 8/8 recipients of the Pfizer and Moderna vaccines, respectively, had S-protein IgG antibodies in their saliva, while IgA was detected in a substantial proportion. These observations may be relevant to vaccine-mediated protection from SARS-CoV-2 infection and disease.

Keywords: COVID-19; RBD; S-protein; SARS-CoV-2; saliva.

ED Figure 1.. Antibody response to the SARS-CoV-2 S-protein in saliva and sera from SARS-CoV-2 vaccine recipients and infected people.

The format of this figure is the same as Figure 1, and shows additional longitudinal profiles for trial participants in Groups 1–4, as indicated.

ED Figure 1.. Antibody response to the SARS-CoV-2 S-protein in saliva and sera from SARS-CoV-2 vaccine recipients and infected people.

The format of this figure is the same as Figure 1, and shows additional longitudinal profiles for trial participants in Groups 1–4, as indicated.

ED Figure 1.. Antibody response to the SARS-CoV-2 S-protein in saliva and sera from SARS-CoV-2 vaccine recipients and infected people.

The format of this figure is the same as Figure 1, and shows additional longitudinal profiles for trial participants in Groups 1–4, as indicated.

ED Figure 2.. Specificity and sensitivity of IgA detection.

Purified human IgG, purified SIgA and recombinant IgA₁ lambda (see Online Methods) were coated on to ELISA plates and detected with the same goat anti-human IgA-HRP conjugate used in the assays to detect saliva and serum IgA S-protein antibodies. The plot shows net OD₄₅₀ values as a function of the amounts of the three antibodies added to the ELISA wells during the coating stage.

Figure 1.. Antibody response to the SARS-CoV-2 S-protein in saliva and sera from SARS-CoV-2 vaccine recipients and infected people.

Each diagram shows S-protein IgA, IgG, and IgM antibody reactivities over the time of sampling. The dates of vaccination are indicated by the variable bars. Representative single-dilution binding data are shown for sera from each category: (A) Pfizer vaccine: Cases 0010, 0046, 0061, 0034. (B) Moderna vaccine: Cases 0016, 0078, 0041, 0059. (C) Control (non-infected): Cases 0016, 0011, 0013. 0020. (D) Infected: Cases 0037, 0063, 0001, 0052 (the latter two were vaccinated). Additional profiles are shown in ED Fig. 1.

Figure 2.. Antibody responses to the SARS-CoV-2 S-protein and RBD-protein in saliva and sera from SARS-CoV-2 vaccine recipients.

The data shown were collated for all vaccine recipients shown in Fig.1A, B and the corresponding panels of ED Fig.1. The longitudinal profiles span a 150-day period before and then ~60 days after the first immunization (day-0, indicated by the vertical black stippled line). They show saliva and serum IgA, IgG, and IgM antibodies against the S-protein (top two rows, as indicated) and the corresponding reactivities with RBD in saliva (bottom row). Recipients of the Moderna vaccine are represented in red, Pfizer in black.

Figure 3.. Relative antibody reactivities with S-protein in saliva and sera.

A reference serum from a SARS-CoV-2 infected person (D56, not part of the NYP-WELCOME cohort; in blue) and serum (in red) and saliva (in black) samples from two recipients of two doses of the Pfizer vaccine (0003, day-29, top row; 0007, day-33, bottom row) were titrated under the conditions of the ELISA used to detect IgA and IgG in saliva. The displacement of the serum and saliva titration curves suggest that the S-protein IgA and IgG titers in saliva are ~1000-fold and ~10,000-fold lower than in sera, respectively.