Detection of Anti‐SARS‐CoV‐2 Mucosal Immunoglobulin A in Clinical Saliva Samples After a Dose of Novavax COVID‐19 Vaccine

ABSTRACT Immunoglobulin (Ig) A acts as a first line of defense against respiratory pathogens. Mucosal IgA in salivary and nasal passages has a rapid response to antigens and can play a protective role against reinfection. The mainstay for analyzing SARS‐CoV‐2 infection and vaccine efficacy has been assessment of serum IgG levels; however, validated assays for assessment of mucosal IgA in clinical samples are necessary as new and adapted measures are generated to combat immune‐evasive viral variants. A mucosal IgA assay was developed and tested through assessment of IgA levels in salivary samples from participants of the 2019nCoV‐314/NCT05973006 study. These participants had previously received ≥ 2 mRNA‐based COVID‐19 vaccinations prior to enrollment and received a single intramuscular study dose of NVX‐CoV2601 (XBB.1.5) or bivalent vaccine (NVX‐CoV2601 + NVX‐CoV2373 [Wuhan]). Salivary samples were collected prior to vaccination on Day 0 and on Day 28 to assess response postvaccination. Both vaccine groups elicited a significant increase in anti‐SARS‐CoV‐2 spike IgA against XBB.1.5. Furthermore, cross‐reactivity by identification of anti‐JN.1 and anti‐Wuhan IgA was also observed. The detection of IgA in clinical mucosal samples using this assay will be a valuable tool in supporting vaccine development.