Background: The Controlled Human Infection for Vaccination Against S. pyogenes, GAS (CHIVAS) human challenge model enables direct appraisal of GAS vaccine candidates and investigation of immunity following GAS upper respiratory tract (URT) infection. We have previously developed novel vaccine antigens (J8 and p*17 ) based on highly-conserved M-protein regions without human tissue cross-reactivity, and a vaccine epitope (K4S2) from the IL-8 protease SpyCEP. Combination vaccines including J8 or p*17 and K4S2 have demonstrated efficacy in pre-clinical studies and will shortly enter Phase 1 clinical trials, to be followed by efficacy studies in the human challenge model.
Methods: We assessed whether experimental human infection with emm75 in the CHIVAS trial generated memory B-cells recognising the vaccine epitopes J8, p*17, and K4S2 in PBMC samples from pre-challenge, and 1- and 6-month timepoints following experimental pharyngitis. We will assess protection against homologous GAS URT infection in HLA transgenic mice using an established pre-incubation challenge model. Antibody binding to different GAS strains and affinity will be assessed in whole-cell and antigen-specific ELISA assay.
Results: High-affinity class-switched antibodies recognizing vaccine epitopes and emm75 were identified in plasma from infected volunteers. Our preliminary data show an increase of emm75-memory B cells IgA+ and IgD+IgM+ at 6 months post-infection. Further analysis will investigate epitope-specific memory B-cell response.
Conclusion: Identification of vaccine antigen-specific circulating memory B-cells and assessment of protection afforded by passive transfer of vaccine antigen-specific antibodies from CHIVAS human challenge participants contributes to proof-of-concept for the efficacy and durability of immune responses to minimum epitope GAS vaccines.