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**Vi-CRM197 + O:2-CRM197** is a bivalent conjugate vaccine candidate developed by the Novartis Vaccines Institute for Global Health (NVGH) to protect against enteric fever caused by *Salmonella Typhi* and *Salmonella Paratyphi A*. It combines **Vi-CRM197**, where the Vi capsular polysaccharide from *S. Typhi* (or recombinant from *Citrobacter freundii* WR7011) is conjugated to CRM197 (a non-toxic mutant diphtheria toxin protein carrier), and **O:2-CRM197**, where the O-specific polysaccharide (O:2 antigen) from *S. Paratyphi A* is conjugated to CRM197 via novel chemistry targeting the 3-deoxy-D-manno-octulosonic acid (KDO) terminus to preserve the antigen chain. The conjugation enhances immunogenicity by converting T-independent polysaccharides into T-dependent antigens, inducing strong, functional serum bactericidal antibodies and IgG responses without immunologic interference between components. Vi-CRM197 has shown promising safety and immunogenicity in Phase 1/2 trials; the bivalent formulation demonstrates correlated killing activity against both pathogens in preclinical models.
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