Salmonella Combination Vaccines: Moving Beyond Typhoid.

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.

The Challenges and Opportunities of Next-Generation Rotavirus Vaccines: Summary of an Expert Meeting with Vaccine Developers.

The 2nd Next Generation Rotavirus Vaccine Developers Meeting, sponsored by PATH and the Bill and Melinda Gates Foundation, was held in London, UK (7-8 June 2022), and attended by vaccine developers and researchers to discuss advancements in the development of next-generation rotavirus vaccines and to consider issues surrounding vaccine acceptability, introduction, and uptake. Presentations included updates on rotavirus disease burden, the impact of currently licensed oral vaccines, various platforms and approaches for next generation rotavirus vaccines, strategies for combination pediatric vaccines, and the value proposition for novel parenteral rotavirus vaccines. This report summarizes the information shared at the convening and poses various topics worthy of further exploration.

The Shigella Vaccines Pipeline.

Shigella is the leading cause of global diarrheal deaths that currently lacks a licensed vaccine. Shigellosis drives antimicrobial resistance and leads to economic impact through linear growth faltering. Today, there is a robust pipeline of vaccines in clinical development which are broadly divided into parenteral glycoconjugate vaccines, consisting of O-antigen conjugated to carrier proteins, and oral live attenuated vaccines, which incorporate targeted genetic mutations seeking to optimize the balance between reactogenicity, immunogenicity and ultimately protection. Proof of efficacy has previously been shown with both approaches but for various reasons no vaccine has been licensed to date. In this report, we outline the requirements for a Shigella vaccine and describe the current pipeline in the context of the many candidates that have previously failed or been abandoned. The report refers to papers from individual vaccine developers in this special supplement of Vaccines which is focused on Shigella vaccines. Once readouts of safety and immunogenicity from current trials of lead candidate vaccines among the target population of young children in low- and middle-income countries are available, the likely time to licensure of a first Shigella vaccine will become clearer.