Background: Pre-challenge, acute, and convalescent samples from the Controlled Human Infection for Vaccination Against S. pyogenes (CHIVAS) pharyngitis model can offer a unique perspective on immune response dynamics. In the initial CHIVAS-M75 dose-finding study, 25 healthy adults were challenged with emm75 S. pyogenes. Colonisation was established in 20/25 participants and acute pharyngitis diagnosed in 19/20 colonised participants. We aimed to systematically characterise antibody responses in saliva samples from CHIVAS-M75.
Methods: We have developed enzyme linked immunosorbent assays (ELISA) to quantify salivary total IgA and antigen-specific IgA titres to 17 S. pyogenes antigens, including type-specific and conserved antigens relevant to vaccine development. To explore the functional impact of these antibodies, we incorporated saliva into an adhesion/internalisation assay using a pharyngeal cell line (Detroit 562).
Results: Total IgA and antigen-specific antibody responses were highly variable, with no correlation between pre-challenge levels and clinical outcome. However, there was an overall increase in antigen-specific IgA in participants who did not develop pharyngitis, compared to participants with pharyngitis. This was independent of changes in total IgA. Initial functional studies have highlighted a saliva concentration-dependent reduction in adhesion.
Conclusions: Experimental human pharyngitis is associated with measurable IgA responses in saliva, even in the absence of colonisation. Combined with recently published saliva cytokine findings, these IgA results highlight the importance of mucosal immune responses for protection against pharyngitis.