Advancing iNTS Vaccines: A Systematic Review of GMMA and OSP Conjugate Platforms

Abstract Invasive non-typhoidal Salmonella enterica (iNTS) causes severe mortality in sub-Saharan Africa, particularly among infants and immunocompromised individuals. Since current typhoid conjugate vaccines target the Vi capsular antigen and offer no cross-protection against Vi-negative iNTS lineages, developing next-generation platforms like generalized modules for membrane antigens (GMMAs) and O-specific polysaccharide (OSP) conjugates is urgent. This systematic review evaluates the distinct immunological hurdles and clinical advancements of these platforms. Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and clinical trial registries up to May ۲۰۲۶ yielded ۲۵ eligible preclinical and clinical studies, assessed using Cochrane ROB۲ and SYRCLE tools. Preclinical findings indicate that overcoming the complement-evasion mechanisms of African ST۳۱۳ lineages requires high-avidity anti-OAg IgG. Advancements show CDAP-linked OSPs with Diphtheria Toxoid carriers significantly outperform Tetanus Toxoid formulations, and aluminum phosphate effectively mitigates immune interference in trivalent formulations. Clinically, the Phase I SALVO trial evaluating a bivalent GMMA vaccine demonstrated an excellent safety profile due to targeted lipid A detoxification. A ۴۰ μg, three-dose regimen induced >۴-fold seroconversion, with serum bactericidal activity peaking ۲۸ days post-vaccination. However, achieving robust immunogenicity in vulnerable groups remains a translational challenge. In conclusion, next-generation iNTS vaccines have successfully entered human trials, exhibiting robust safety and bactericidal efficacy against African lineages. These promising Phase I data strongly support advancing to Phase II/III efficacy trials. Future efforts must prioritize establishing immunological correlates of protection and optimizing immunization schedules for seamless integration into routine pediatric programs in low-resource settings

کلیدواژه ها:

Invasive non-typhoidal Salmonella ، GMMA vaccines ، Conjugate platforms