Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals

Abstract

Mucosal immune responses are critical to prevent respiratory infections but it is unclear to what extent antigen specific mucosal secretory IgA (SIgA) antibodies are induced by mRNA vaccination in humans. We analyzed, therefore, paired serum and saliva samples from study participants with and without COVID-19 at multiple timepoints before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Our results suggest that the level of mucosal SIgA responses induced by mRNA vaccination depend on pre-existing immunity. Indeed, vaccination induced only a weak mucosal SIgA response in individuals without pre-existing mucosal antibody responses to SARS-CoV-2 while SIgA induction after vaccination was efficient in COVID-19 survivors. Our data indicate that vaccinated seropositive individuals were able to swiftly induce relatively high anti-spike SIgA responses by boosting pre-existing mucosal immunity. In contrast, seronegative individuals did not have pre-existing anti-SARS-CoV-2 or cross-reacting anti-HCoV SIgA antibodies prior to vaccination, and, thus, little or no anti-SARS-CoV-2 SIgA antibodies were induced by vaccination in these individuals.

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

“…Our findings of IgA in the saliva are consistent with recent reports showing that after two doses of BNT162b2 or mRNA-1273 anti-Spike and anti-RBD Ab could be detected in saliva 17-19 . We also distinguish between locally produced and systemically derived IgA using secretory component detection.…”

Multiplex Antibody Analysis of IgM, IgA and IgG to SARS-CoV-2 in Saliva and Serum From Infected Children and Their Close Contacts

“…This non-invasive field deployable antibody screening could be useful to establish the percentage of people who have been exposed to SARS-CoV-2 in epidemiological surveys, and to assess the longitudinal maintenance of antibodies (40), particularly in children who were not initially prioritized in 2021 for COVID-19 vaccination. Furthermore, considering the significant correlation between saliva and serum/plasma of antibody levels to S, it could also be an attractive tool to monitor induction and maintenance of vaccine responses, including to variants of concern, as part of large-scale immunization campaigns (35,(41)(42)(43).…”

Protection of prior natural infection compared to mRNA vaccination against SARS-CoV-2 infection and severe COVID-19 in Qatar

“…These findings may be explained by different roles for mucosal immunity in the protection. 14,15 While natural infection was associated with stronger protection, vaccination remains the safest and optimal tool of protection against infection and COVID-19 hospitalization and death.…”

“…5,6 A growing number of studies suggests that there are differences in the level and durability of protection of natural infection versus vaccination. [7][8][9][10][11] These differences may arise from differences in the mechanism of action, 12,13 from mucosal immunity, 14,15 volume and nature of neutralizing antibody titers, 12,16,17 or circulating variants. [18][19][20][21][22] Protection conferred by natural infection versus vaccination has not been investigated in rigorously controlled studies that directly compare them.…”

“…5,6 A growing number of studies suggests that there are differences in the level and durability of protection of natural infection versus vaccination. 7-11 These differences may arise from differences in the mechanism of action, 12,13 from mucosal immunity, 14,15 volume and nature of neutralizing antibody titers, 12,16,17 or circulating variants. 18-22…”