Strategy for a Broad-Spectrum Vaccine Against Non-Typhoidal Salmonella

OverviewOn screening sub-Saharan African residents over the last decade for signs of invasive bacterial infection, a high incidence of non-typhoidal Salmonella (NTS) infections was discovered, and these cases were associated with antibiotic resis…

Overview

On screening sub-Saharan African residents over the
last decade for signs of invasive bacterial infection, a high incidence
of non-typhoidal Salmonella (NTS) infections was discovered, and these
cases were associated with antibiotic resistance and a high mortality of
20-30%. The invasive strains of NTS are dominated by Salmonella
Typhimurium and Salmonella Enteritidis. In more industrialized
countries, NTS causes outbreaks of gastroenteritis (1.4 million cases
and 400 deaths in the U.S. annually), such as the illness from
contaminated peanut butter in early 2009. These outbreaks are increasing
in frequency in the industrialized world and expected to increase in
severity, particularly affecting young infants, the elderly, and those
who are immunocompromised. To address the NTS disease problem, UMB
researchers have developed a multivalent vaccine strategy: (1) a live
oral vaccine with specific attenuating mutations; and (2) a conjugate
vaccine consisting of bacterial polysaccharide linked to flagella
protein from the same strain. The live NTS vaccine strain is also used
to produce the conjugate vaccine, and the specific genetic mutations
provide manufacturing advantages for enhanced safety and high yields.
The researchers are concurrently testing a few candidate vaccine strains
that have slightly different mutations. The live and conjugate vaccines
were shown to be highly immunogenic and well tolerated in mice. In
studies challenging mice with a lethal dose of NTS pathogen, the
vaccinated mice were protected versus controls. What may provide the
best overall protection is to administer a priming dose of live vaccine
followed by a boost with the conjugate vaccine.

Applications

Vaccinating children under 5 years old in the
developing world Vaccinating the at-risk population in the
industrialized world, including the elderly

Advantages

FIRST VACCINE OF ITS KIND, as no licensed NTS vaccine currently exists

Stage of Development

Preclinical studies demonstrate vaccine
strains are highly immunogenic and well tolerated and, importantly,
protect mice from a lethal challenge with NTS pathogen. Studies continue
on the conjugate vaccine to determine its optimal composition.

R&D Required

Further preclinical studies, with optimization of vaccine strategy, followed by clinical development.