Background
The primary route of infection for SARS Cov-2 is through inhalation. The virus can infect cells along the mucosal tract from nares and mouth to gut. The impact of the mucosal immune response in control of the infection and protection from reinfection unclear. It is unknown whether a nasal vaccine would provide better protection. Our objective was to determine the IgG and IgA antibody levels in the saliva of a subset of persons participating in a longitudinal observational study of COVID immunity and to compare responses in those with vaccine only and those with hybrid immunity.
Methods
A random sample of 180 persons participating in the STOPCoV study (n=1286, mean follow up 1.5 years, mean 5 vaccine doses) were invited to participate in a sub-study of mucosal immunity. Samples of saliva were collected in December 2022 and April 2023. We analyzed the levels of IgG and IgA to spike protein and receptor binding domain (RBD) to the Wuhan ancestral strain and Omicron variant in 51 participants. We excluded individuals who had a breakthrough infection or received a vaccine dose in the interval between testing periods. We selected those with hybrid immunity who had a breakthrough infection in the previous 6 months. Regression for continuous outcomes (antibody levels) and survival outcomes (subsequent breakthrough infection) was used.
Results
Participants with hybrid immunity were more likely to have detectable IgA antibody to RBD than those with vaccine only immunity to both the Wuhan ancestral strain (100%, 79%) p=.04 and the Omicron variant (93%, 74%) p=.11. Similar trends were seen with IgA antibody to spike to Wuhan (94%, 82%) p=.24 and all has positive IgA antibody to spike to Omicron . Significant decay was seen with IgA antibody to RBD protein to both Wuhan and Omicron between the two sampling periods. Neither salivary IgA positivity nor the relative level of IgA antibody to Omicron was predictive of protection from breakthrough infection over the subsequent year, although receipt of an additional COVID vaccine was.
Conclusions
Hybrid immunity was associated with higher proportions of individuals having positive mucosal IgA and IgG antibodies to spike and RBD proteins of SARSCo -2 but these decayed with time and were not associated with protection from a breakthrough infection in the following year.
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