Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva

Abstract

The approved Pfizer and Moderna mRNA vaccines are well known to induce serum antibody responses to the SARS-CoV-2 Spike (S)-protein. However, their abilities to elicit mucosal immune responses have not been reported. Saliva antibodies represent mucosal responses that may be relevant to how mRNA vaccines prevent oral and nasal SARS-CoV-2 transmission. Here, we describe the outcome of a cross-sectional study on a healthcare worker cohort (WELCOME-NYPH), in which we assessed whether IgM, IgG, and IgA antibodies to the S-protein and its receptor-binding domain (RBD) were present in serum and saliva samples. Anti-S-protein IgG was detected in 14/31 and 66/66 of saliva samples from uninfected participants after vaccine doses-1 and -2, respectively. IgA antibodies to the S-protein were present in 40/66 saliva samples after dose 2. Anti-S-protein IgG was present in every serum sample from recipients of 2 vaccine doses. Vaccine-induced antibodies against the RBD were also frequently present in saliva and sera. These findings may help our understanding of whether and how vaccines may impede SARS-CoV-2 transmission, including to oral cavity target cells.

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, 0044, 0046, 0061. (B) Moderna vaccine: Cases 0009, 0040, 0041, 0059. (C) Control (non-infected): Cases 0006, 0011, 0013. 0020. (D) Infected: Cases 0001, 0015, 0051, 0052. Additional profiles for groups 1-4 are shown in Supplemental Figure 1.

Figure 2.

Antibody responses to the SARS-CoV-2 S-protein in saliva and sera from SARS-CoV-2 vaccine recipients. The data shown were collated for all vaccine recipients shown in Figure 1A, B and the corresponding panels of Supplemental Figure 1. The longitudinal profiles span a 150-day period before and then ~100 days after the first immunization (day-0, indicated by the vertical black stippled line). A) Saliva and B) serum IgA, IgG, and IgM antibodies against the S-protein; C) Saliva IgA, IgG, and IgM antibodies against the RBD (after vaccine dose 2 only). Recipients of the Moderna vaccine are represented in red, Pfizer in black.

Figure 3.

Specificity and sensitivity of IgA detection. Purified human IgG, purified SigA, and recombinant, dimeric IgA₁ lambda were coated onto 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 (+/− SEM) as a function of the logarithmic concentrations of the 3 antibodies added to the ELISA wells during the coating stage.

Figure 4.

Antibody response to the common cold CoV S-proteins in saliva and sera from participant 0022. A) The format of this panel is the same as Figure 1 and shows data derived using the SARS-CoV-2 S-protein. B) The panels show saliva or serum IgA or IgG antibody responses to S-proteins from the endemic CoVs 229E, HKU1, NL63, and OC43, in comparison to SARS-CoV-2, as indicated.

Figure 5.

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 2 recipients of 2 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 end-point titers in saliva are ~1000-fold and ~10,000-fold lower than in sera, respectively.