Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection

Abstract

SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic. Approved mRNA COVID-19 vaccines are well known to induce a serum antibody responses against the spike protein and its RBD. Mucosal immunity plays a major role in the fight against COVID-19 directly at the site of virus entry; however, vaccine abilities to elicit mucosal immune responses have not been reported. We detected anti-SARS-CoV-2 IgA-S1 and IgG-RBD in three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection) on serum, saliva, and nasal secretions using two commercial immunoassays (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD). Our results show that the mRNA BNT162b2 vaccine Comirnaty (Pfizer/BioNTech, New York, NY, USA) determines the production of nasal and salivary IgA-S1 and IgG-RBD against SARS-CoV-2. This mucosal humoral immune response is stronger after the injection of the second vaccine dose compared to subjects recovered from COVID-19. Since there is a lack of validated assays on saliva and nasal secretions, this study shows that our pre-analytical and analytical procedures are consistent with the data. Our findings indicate that the mRNA COVID-19 vaccine elicits antigen-specific nasal and salivary immune responses, and that mucosal antibody assays could be used as candidates for non-invasive monitoring of vaccine-induced protection against viral infection.

Immunogenicity and safety of COVID-19 vaccination in patients with primary Sjögren’s syndrome

“…We observed no increase in anti-S1 and anti-RBD IgA levels. In contrast, some studies did show a mucosal IgA response,27 28 although this was often weaker than the mucosal IgG and systemic antibody response. However, some other studies also reported no mucosal IgA response following vaccination 29 30…”

BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

“…We have not measured the presence of SARS‐CoV‐2‐specific IgG and IgA in other mucosal fluids. However, two recent publications show that SARS‐CoV‐2‐specific IgG and IgA are both detected also in nasal fluid samples (Chan et al , 2021; Guerrieri et al , 2021), even though at lower levels than in the saliva (Guerrieri et al , 2021). The fact that SARS‐CoV‐2‐specific IgA2 were not detected in the saliva of vaccinated subjects supports the need for mucosal vaccination and/or boosting strategies that promote anti‐SARS‐CoV‐2 S‐IgA, which are more potent at neutralizing the virus than IgGs thanks to their mechanism of pathogen clearance called immune exclusion (Mantis et al , 2011; Wang et al , 2021).…”

Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

“…First, we have not yet developed appropriate assays for mucosal immune responses to deepen our understanding of the immune advantage of aerosolized Ad5-nCoV. Saliva IgA antibodies were detected in some BNT162b2 vaccine recipients (25, 26) , but whether IgA was exuded from serum or produced by a local mucosal immune response could not be determined. More assays need to be developed to analyze local mucosal immune responses, including secretory IgA antibodies and local cellular immune responses.…”

“…First, we have not yet developed appropriate assays for mucosal immune responses to deepen our understanding of the immune advantage of aerosolized Ad5-nCoV. Saliva IgA antibodies were detected in some BNT162b2 vaccine recipients (25,26) Boosters probably increase vaccine effectiveness against infection with and transmission of the SARS-CoV-2 Omicron variant.…”