Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection

Abstract

Vaccines against SARS-CoV-2 administered via the parenteral route (intra-muscular = i.m.) are effective at preventing COVID-19 in part by inducing neutralizing antibodies in the blood. The first line of defense against SARS-CoV-2 is in the upper respiratory tract, yet we know very little about whether COVID-19 vaccines induce immunity in this compartment, if at all. We analysed salivary antibodies against the SARS-CoV-2 Spike protein and its receptor binding domain (RBD) following 2 i.m. injections of either BNT162b2 or mRNA-1273 vaccines. Salivary anti-Spike/RBD IgG was detected after 1 dose and increased further after dose 2, reflecting the systemic immune response. Interestingly, salivary anti-Spike/RBD IgA associated with the secretory component (sIgA) was detected in nearly all vaccinated participants after one dose of mRNA vaccine, with anti-Spike sIgA diminishing after dose 2. Vaccination with ChAdOx1-S (Ad) followed by mRNA induced similar levels of salivary anti-Spike/RBD IgG and IgA, and both mRNA/mRNA and Ad/mRNA regimes provoked modest neutralizing capacity in this biofluid. Our results demonstrate that SARS-CoV-2 mRNA/mRNA and Ad/mRNA vaccination induces antibodies in the saliva, and in response to one dose of mRNA, a compartmentalized and transient antigen-specific sIgA response is generated that does not correlate with systemic immunity.

Intramuscular SARS-CoV-2 vaccines elicit varying degrees of plasma and salivary antibody responses as compared to natural infection

“…We found that these vaccines generated neutralizing activity in the saliva comparable to natural infection, with peak levels after the second dose in those individuals which had high levels of IgA in their saliva as determined by ELISA. The SPIKE and RBD binding IgA antibodies in these samples were shown to have secretory component as would be expected of dimeric IgA in the saliva (44), and importantly, dimeric IgA has been shown to be a more potent neutralizer than either IgG or monomeric IgA (55).…”

“…In the ELISA assays used by the Gommerman lab to quantify salivary anti-RBD levels, samples were pre-adsorbed with streptavidin to eliminate non-specific streptavidin binding IgA in saliva as previously described (33). The lack of non-specific binding in pre-adsorbed samples is reflected in their low level of IgA signal derived from pre-COVID-19 saliva (data not shown, please see accompanying manuscript) (44). Maximum infection and FRNT50 quantification of neutralizing activity in 1dose and "A Low'' 2-dose groups all had significantly higher neutralizing activity compared to Baseline (Figures 4D, 4E), as well as comparable neutralizing activity to convalescent saliva collected by OraSure (Figures 1G, 1H).…”

“…Furthermore, researchers are still learning about the immune components in saliva. For example, the method of assay may require special handling steps such as the pre-adsorption step with materials not containing the RBD or spike protein targets to reveal specific antibodies to the viral targets, as shown by the Gommerman lab ELISA assay (33,44) and others (45). One limitation of our observational study is that the extent that salivary antibodies contribute to vaccine efficacy remains unknown, and further research should consider how salivary antibodies may explain some differences in observed vaccine efficacy.…”

Prevention of host-to-host transmission by SARS-CoV-2 vaccines

“…16,17 Additionally, IgA and IgG neutralising antibodies, including highly effective secreted dimeric IgA, have been observed in the saliva of patients vaccinated with BNT162b1 or mRNA-1273. 15,[18][19][20] These studies show variable capacity among the parenteral vaccines to induce sterilising immunity at the mucosa, with ChAdOx1 vaccine being potentially less effective than the mRNA vaccines. Factors potentially influencing whether these vaccines induce mucosal sterilising immunity include the mechanism of the vaccine and the quantity and quality of circulating neutralising antibodies generated.…”

Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain

“…Therefore, studies detecting IgA in addition to IgG in saliva will help to better understand the dynamics of COVID-19 mucosal immunity. Thus, saliva antibody assays could be valuable to monitor vaccine take and correlates of protection when inhaled or intranasal boosters become available [34].…”