GMMA-based vaccine candidates against invasive nontyphoidal salmonellosis elicit bactericidal antibodies against a panel of epidemiologically relevant Salmonellae

Systemic disease caused by nontyphoidal <i>Salmonella</i> (NTS) represents a major cause of death and morbidity, especially in young children in sub-Saharan Africa. No licensed vaccine is yet available, and an increase in antimicrobial resistance makes the development of a vaccine a global health priority. We are developing a bivalent formulation of <i>Salmonella</i> Typhimurium and <i>Salmonella</i> Enteritidis generalized modules for membrane antigens (GMMA)-based vaccine (iNTS-GMMA) and a trivalent formulation (iNTS-TCV) in which iNTS-GMMA is combined with the WHO-prequalified TYPHIBEV (Biological E, India) vaccine to prevent typhoid fever in addition to invasive NTS (iNTS) disease. Here, we measured the ability of antibodies induced by iNTS-GMMA and iNTS-TCV formulations in mice and rabbits to kill a broad panel of <i>Salmonella in vitro</i> in a complement-mediated fashion. These organisms include those causing invasive disease in Africa and Southeast Asia, global representatives causing gastroenteritis and other <i>S</i>. <i>enterica</i> serovars in addition to <i>S.</i> Typhimurium and <i>S.</i> Enteritidis. We characterized the O-antigen of the panel of isolates and demonstrated the sera functionality in both animal species against all isolates, providing evidence of the potential broad coverage of both GMMA-based formulations, which are currently undergoing testing in Phase I/II clinical trials.