Immunogenicity of a Bivalent Typhoid-Paratyphoid Conjugate Vaccine Against Diverse Salmonella Paratyphi A Isolates.

Abstract

In a first-in-human phase-1, randomized, controlled trial, a bivalent conjugate vaccine (Vi-CRM197+O:2 CRM197) elicited robust IgG and bactericidal activity against vaccine-homologous Salmonella Paratyphi A strain. To further characterize the immune response, we assessed O:2 antigen-specific IgA and IgM responses as markers of mucosal immunity and early immune activation, and evaluated serum bactericidal activity against diverse S. Paratyphi A isolates. The trial (NCT05613205) was conducted in three steps. For this exploratory analysis, 46 participants (mean age 27.2 years; 67.4% women) from Step-2 who received two full doses of Vi-CRM197+O:2 CRM197 vaccine with and without Alum (Aluminum hydroxide) 169 days apart were considered. O:2-specific IgA/IgM responses and bactericidal antibodies were assessed. Geometric mean titers and concentrations, and within-participant geometric mean ratios were calculated. Both formulations induced strong anti-O:2 IgA/IgM responses and bactericidal activity, with higher responses in the non-adjuvanted group. At Day-29 post-dose 1, IgA rose 74.14- and 16.65-fold (without vs. with Alum), remaining well above baseline through Day-197. The non-adjuvanted formulation induced significantly higher IgA responses and bactericidal activity at Day-29 (p <0.05). Anti-O:2 IgM strongly correlated with bactericidal antibodies against homologous and heterologous strains. The vaccine effectively induced O:2-specific IgA, IgM, and bactericidal antibodies against diverse S. Paratyphi A isolates, indicating potential broad protection.