# Multivalent vaccines for invasive Salmonella disease: need, rationale, and immunological foundations

## TL;DR

This paper discusses the need for multivalent Salmonella vaccines to combat various strains, especially in regions with high infection rates and antibiotic resistance.

## Contribution

The paper provides a rationale for multivalent vaccine design by analyzing pathogenesis and immunity to Salmonella.

## Key findings

- Salmonella infections are a major global health issue, especially in sub-Saharan Africa and Asia.
- Current vaccines target only S. Typhi, but multivalent vaccines are being developed for broader coverage.
- Choosing the right antigens is crucial for effective multivalent Salmonella vaccines.

## Abstract

Salmonella enterica infections are a major cause of morbidity and mortality worldwide, especially in sub-Saharan Africa and in the Asian continent, and are increasingly associated with antimicrobial resistance. Salmonella enterica serovars Typhi and Paratyphi A, B, and C cause enteric fever, while non-typhoidal Salmonella serovars (usually Typhimurium and Enteritidis) cause mainly gastroenteritis which can lead to systemic infections. Vaccines are only licensed against S. Typhi, but different combinations are in clinical development to prevent S. Typhi and S. Paratyphi A or S. Typhi and non-typhoidal Salmonella. Here, we describe elements of the pathogenesis of and immunity to Salmonella that are critical to guide the rational design of vaccines. We highlight how the choice of appropriate immunogenic and protective antigens would be essential to achieve the maximum coverage of serovars in a multivalent Salmonella vaccine. The principal vaccines under development at the preclinical and clinical stages are described, together with considerations on the technical and clinical feasibility of moving combination vaccines toward licensure.