Safety and colonization of two novel VirG(IcsA)-based live Shigella sonnei vaccine strains in rhesus macaques (Macaca mulatta).
Shigella are gram-negative bacterium that cause bacillary dysentery (shigellosis). Symptoms include diarrhea and discharge of bloody mucoid stools, accompanied by severe abdominal pain, nausea, vomiting, malaise, and fever. Persons traveling to regions with poor sanitation and crowded conditions become particularly susceptible to shigellosis. Currently a vaccine for Shigella has not been licensed in the United States, and the organism quickly becomes resistant to medications. During the past 10 y, several live attenuated oral Shigella vaccines, including the strain WRSS1, have been tested in humans with considerable success. These Phase I vaccines lack the gene for the protein VirG also known as IcsA, which enables the organism to disseminate in the host target tissue. However, 5% to 20% of the vaccinated volunteers developed mild fever and brief diarrhea, and the removal of additional virulence-associated genes from the vaccine strain may reduce or eliminate these side effects. We administered 2 Shigella sonnei vaccines, WRSs2 and WRSs3, along with WRSS1 to compare their rates of colonization and clinical safety in groups of 5 rhesus macaques. The primate model provides the most physiologically relevant animal system to test the validity and efficacy of vaccine candidates. In this pilot study using a gastrointestinal model of infection, the vaccine candidates WRSs2 and WRSs3, which have additional deletions in the enterotoxin and LPS modification genes, provided better safety and comparable immunogenicity to those of WRSS1.
The Walter Reed Army Institute of Research, Naval Medical Research Center, Silver Spring, MD, USA. todd.collins@us.army.mil
Todd A
TA
Collins
Shoshana
S
Barnoy
Shahida
S
Baqar
Ryan T
RT
Ranallo
Kevin W
KW
Nemelka
Malabi M
MM
Venkatesan
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001835:Body Weight; D017931:DNA Primers; D004269:DNA, Bacterial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000097:blood / Q000276:immunology; D005243:Feces / Q000382:microbiology; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D016133:Polymerase Chain Reaction; D012449:Safety; D022281:Shigella Vaccines / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology* / Q000592:standards; D014157:Transcription Factors / Q000276:immunology*; D014195:Travel
D001426:Bacterial Proteins; D017931:DNA Primers; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D022281:Shigella Vaccines; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri