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

ABSTRACT: Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA-based vaccine-encoding SARS-CoV-2 full-length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS-CoV-2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease-susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS-CoV-2-naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

SUBMITTER: Darwich A

PROVIDER: S-EPMC9081904 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Darwich Abbass A Pozzi Chiara C Fornasa Giulia G Lizier Michela M Azzolini Elena E Spadoni Ilaria I Carli Francesco F Voza Antonio A Desai Antonio A Ferrero Carlo C Germagnoli Luca L Mantovani Alberto A Rescigno Maria M

EMBO molecular medicine 20220419 5

Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA-based vaccine-encoding SARS-CoV-2 full-length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS-CoV-2 previously exposed subjects, paralleling the developme ...[more]

PMID: 35393790

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Project description:The behavioral immune system (BIS) comprises manifold mechanisms, that may assist the physiological immune system (PIS) in counteracting infection and can even reduce the risk of contagion. Previous studies have found initial evidence for possible interactions between the two systems. However, most of these findings were correlative and have not been replicated. Further, none of these studies examined whether disease stimuli that indicate an enhanced airborne transmission risk may trigger a different immune response in comparison to stimuli that predominantly evoke core disgust. In the present study, we employed a video-priming approach to get further insight in the influence of the perception of disgust- and disease-related stimuli on the rapid physiological immune response, as indicated by changes of secretory immunoglobulin A (S-IgA) in saliva. We created three video primers that represented different categories of disgust- and/or disease-associated content. Two of the videos showed disease-related situations that were associated with contagious respiratory virus infections, varying in concealment of aerosols. The third video incurred no heightened airborne contagion risk, but comprised situations that are known to elicit core disgust, such as rotten foods, decaying animal carcasses, or cockroaches. A fourth video acted as control showing landscape impressions. The different video primers varied in their contagion risk and disgust-evoking potential. Given the role of S-IgA in the mucosal immune defense, we expected differences in the S-IgA response between the two videos indicating a heightened airborne contagion risk and the core disgust video, with the highest S-IgA to occur after the aerosol video. For this, we used the data of 107 healthy participants in a between-subjects design with the four video primers. We found a significant increase of S-IgA in response to both the disease- and the disgust-related videos, which correlated positively with the perceived contagion risk of the displayed situations. Nevertheless, there was no significant difference in the increase between the three disease- and disgust-related videos. We also found that people with a high contamination disgust produced less S-IgA in such situations, which is a hint for a compensating relationship between the BIS and PIS. Our observations suggest that the mere visual perception of videos showing realistic situations of an increased contagion risk can elicit a heightened release of salivary antibodies. Highlights • Realistic videos of respiratory diseases are efficient to trigger immune responses.• Secretory Immunoglobulin A (S-IgA) in saliva increases after video-priming.• S-IgA increase is positively correlated with perceived contagion risk.• S-IgA increase is inversely correlated with the trait contamination disgust.

Project description:BackgroundOn July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness.MethodsWe extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors.ResultsAt least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1).ConclusionsIn this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.

Project description:BackgroundTo date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination.MethodsSamples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva.FindingsAfter eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001).InterpretationThe BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant.FundingThis work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.

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

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

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