Study reports potently neutralizing mucosal IgA in saliva of BNT162b2 vax recipients

The ability of the immune system to prevent the replication and subsequent transmission of pathogens is referred to as ‘sterilizing immunity.’ Primary infection with viral pathogens such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can elicit sterilizing mucosal and systemic immunity, which is activated following secondary exposure to the pathogen at mucosal surfaces.

Vaccination mimics certain aspects of viral infection to train the immune system for future encounters with the actual pathogen. Aside from disease and mortality prevention, the ultimate purpose of a vaccination campaign is to create a strong sterilizing effect, lessen the carrier state, and break the transmission cycle in the population.

About the study
An independent enzyme-linked immunosorbent assay (ELISA) measurement of anti-RBD IgG and anti-RBD IgA in serum samples collected from pre-COVID (n=51), BNT162b2 vaccinee’s (n=17), and post-COVID-19 (n=22) convalescents was used to analyze humoral immune response and to detect transitory secretory dimeric IgA in the saliva of all vaccinees.

The potent neutralizing activity of the humoral component of mucosal defense, as well as its kinetic profile, were investigated. A methodology for quantitative comparison of immune reactivity and neutralization for humoral IgG and IgA responses in serum and saliva in molar equivalents was also developed.

A uniform approach for assessing antibody response that may be used universally, easing standardization in diagnostics and monitoring practices, decision-making in patient treatment, and comparative vaccine evaluations, was also submitted.

Study findings
Vaccinee saliva was found to contain transitory anti-RBD dimeric secretory IgA with strong neutralizing activity, as explained by its tetravalent nature. Polyvalent IgA was proposed to be a major mediator of powerful neutralizing activity in vaccinee saliva, and their levels did not alter after IgG depletion. Thus, reducing salivary IgA eliminated vaccine-induced neutralization.

Comparatively, in serum, IgG was the dominant neutralizing isotype, as demonstrated by its removal that resulted in a loss of neutralization. Surprisingly, and in contrast to the condition in saliva, remaining serum IgA lacked appreciable neutralizing activity, despite its substantially larger concentration that was approximately 30-fold higher in serum as compared to its levels in saliva.

The 50% neutralization capacity (NT50) molar measurements normalized to the binding reactivity values and greatly favored the stronger neutralization by salivary IgA. Anti-RBD IgA remained in the saliva for an extended duration after immunization, wherein it peaked two to four months and diminished only five to six months later, thus significantly outliving serum anti-RBD IgA.

The observation of interaction modes between surface SARS-CoV-2 lattice and mucosal dimeric IgA as compared to monomeric IgG and IgA in blood circulation indicated the importance of using lattice design to improve spatial surface-mimicry in next-generation subunit vaccines. To this end, mRNA-based vaccines allow host cells to display the natural configuration of SARS-CoV-2 spike membranous lattice upon its expression.

Significance
Overall, the results of the current study demonstrate that BNT162b2 vaccination causes a five-month transitory accumulation of anti-RBD IgA in the saliva, extending beyond the time range of detectable circulatory IgA. The researchers suggest that the polymeric origin of the salivary IgA molecules was responsible for the remarkably high specific neutralizing activity, thereby indicating that salivary anti-RBD IgA might represent a general nasopharyngeal humoral component of mucosal defense. News Medical