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. 2023 Jun 2;10(Suppl 1):S58-S66.
doi: 10.1093/ofid/ofad041. eCollection 2023 May.

Salmonella Combination Vaccines: Moving Beyond Typhoid

Calman A MacLennan  1   2 , Jeffrey Stanaway  3 , Stephanie Grow  1 , Kirsten Vannice  1 , A Duncan Steele  1
Affiliations

Salmonella Combination Vaccines: Moving Beyond Typhoid

Calman A MacLennan et al. Open Forum Infect Dis. .

Abstract

There is now a robust pipeline of licensed and World Health Organization (WHO)-prequalified typhoid conjugate vaccines with a steady progression of national introductions. However, typhoid fever is responsible for less than half the total global burden of Salmonella disease, and even less among children aged <5 years. Invasive nontyphoidal Salmonella disease is the dominant clinical presentation of Salmonella in Africa, and over a quarter of enteric fever in Asia is due to paratyphoid A. In this article, we explore the case for combination Salmonella vaccines, review the current pipeline of these vaccines, and discuss key considerations for their development, including geographies of use, age of administration, and pathways to licensure. While a trivalent typhoid/nontyphoidal Salmonella vaccine is attractive for Africa, and a bivalent enteric fever vaccine for Asia, a quadrivalent vaccine covering the 4 main disease-causing serovars of Salmonella enterica would provide a single vaccine option for global Salmonella coverage.

Keywords: Salmonella; nontyphoidal; paratyphoid; typhoid; vaccines.

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Conflict of interest statement

Potential conflicts of interest. C. A. M. is an inventor of the Vi-CRM197 typhoid conjugate vaccine (US patent 2016/0263213 A1, “Typhoid Conjugate Vaccines,” current assignee: GlaxoSmithKline Biologicals SA) and the bivalent nontyphoidal Salmonella generalized modules for membrane antigens vaccine, and is a former employee of the Novartis Vaccines Institute for Global Health. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Salmonella combination vaccine pipeline including licensed and World Health Organization–prequalified typhoid conjugate vaccines, monovalent paratyphoid A vaccines in clinical development, and potential quadrivalent Salmonella vaccines. Arrowed boxes indicate ongoing development. Abbreviations: 1V, monovalent; 2V, bivalent; 3V, trivalent; 4V, quadrivalent; BBIL, Bharat Biotech International Ltd; BCH, Boston Children's Hospital; BioE, Biological E; GMMA, generalized modules for membrane antigens; GVGH, GlaxoSmithKline Vaccines Institute for Global Health; IVI, International Vaccine Institute; LIBP, Lanzhou Institute of Biological Products; NIH, National Institutes of Health; NTS, nontyphoidal Salmonella; PQ, prequalified; SEn, Salmonella Enteritidis; STm, Salmonella Typhimurium; SII, Serum Institute of India; TCV, typhoid conjugate vaccine; UMD, University of Maryland; WHO, World Health Organization.
Figure 2.
Figure 2.
Deaths and disability-adjusted life-years attributable to Salmonella enterica in children aged <5 years and all ages by disease type and geographic region. From Global Burden of Disease 2019 enteric and diarrheal disease burden estimates [30, 31]. Abbreviations: DALYs, disability-adjusted life-years; dNTS, diarrheal nontyphoidal Salmonella disease; iNTS, invasive nontyphoidal Salmonella disease.
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