Completed Infection & Immunity Pregnancy, Children & Inherited Conditions

Vaccines to prevent invasive non-typhoidal Salmonella infections in infants and young children in sub-Saharan Africa.

Funder Wellcome Charity-funded
Recipient organisation University of Maryland
Funding £2.5M
Period May 2012 — Aug 2020

In plain English

AI plain-English summary

Every year, invasive non-typhoidal Salmonella infections kill 20 to 30 percent of the African children who contract them. No licensed human vaccine exists against these strains, which cause bloodstream infections and meningitis. The researchers aim to change that by developing two vaccine candidates against Salmonella Typhimurium, the strain responsible for most cases. One candidate is a live oral vaccine built from an invasive Malian strain with two independent attenuating mutations. The other is a parenteral conjugate vaccine that links the bacterium’s core-O polysaccharide to flagellar protein monomers, which double as an adjuvant. To produce the conjugate components safely and at scale, the team engineered a bacterial strain that hyperexpresses and secretes non-polymerising flagellin monomers into the growth medium. If these vaccines succeed in Phase I clinical trials in the USA, they could eventually protect infants and young children across sub-Saharan Africa from a disease that currently kills a fifth to a third of those infected.

View original technical description
Non-typhoidal Salmonella (NTS) are a major cause of invasive (septicaemia & meningitis) disease in Africa and 20-30% of affected children die. Salmonella Typhimurium and S. Enteritidis cause 80-90% of these infections. There are no licensed human vaccines against NTS. Our ultimate goal is to develop a Typhimurium/Enteritidis vaccine to protect young children and high-risk adults in Africa against NTS. Focusing initially on Typhimurium, we propose to develop and bring to clinical trials two Typhimurium vaccine candidates, each representing a strategy (live oral versus parenteral conjugate) that has led to licensed vaccines against typhoid fever (caused by Salmonella Typhi). Our live oral S. Typhimurium vaccine (from an invasive Malian strain) carries independently attenuating mutations in both guaBA and clpX. Our conjugate links Typhimurium core-O polysaccharide to flagellar protein monomers (a vaccine antigen with adjuvant properties). Our engineered reagent strain, deleted in guaBA, clpPX, fljB and fliD, hyperexpresses and secretes into the media flagellin monomers that cannot polymerise. This reagent strain was specifically created to allow safe, large-scale fermentation and high yields of both conjugate components. We will test both vaccines in Phase I clinical trials in the USA.

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Researchers

Myron Levine (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Preventing Invasive Salmonella Disease in Africa
A Phase 1 Clinical Study to Determine the Safety and Immunogenicity of a Novel GMMA Vaccine Against Invasive Non-Typhoid Salmonella
Age-descending Phase 2 trial to assess safety and immunogenicity of a Trivalent Salmonella (S. Enteritidis, S. Typhimurium, S. Typhi Vi) Conjugate Vaccine for sub-Saharan Africa
The Development of a non-typhoidal Salmonella human challenge model: A safety and dose escalation study.
Advancing a GMMA-based vaccine against invasive non-typhoidal salmonellosis through Phase 1 trial in Europe and sub-Saharan Africa

Original classification

Strategic Translation Award

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