Abstract

Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are currently under development.

Highlights

  • Follow this and additional works at: https://ecommons.aku.edu/coe-wch Part of the Maternal and Child Health Commons, and the Women's Health Commons

  • Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally

  • NTS causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children

Read more

Summary

General approaches to vaccine development for low- and middle-income markets

Proof-of-principle studies have demonstrated efficacy, in animal models, of live-attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of Salmonella Typhimurium and Salmonella Enteritidis. The development of recombinant or purified protein vaccines based on surface or outer membrane protein antigens, such as flagellin and porins OmpC, F and D offer the potential for broadspectrum coverage due to targeting of conserved antigens. Programmatic field implementation in children could integrate directly with existing Expanded Program on Immunization schedules, potentially at 6, 10, and 14 weeks, or at 9 months concomitant with measles vaccination. This schedule will allow for programmatic introduction, as well as will enable children to be protected at an earlier age when they are at higher risk of disease. NTS vaccines could target the elderly who experience a high case-fatality rate of up to 50%

Biological feasibility for vaccine development
Technical and regulatory assessment
Findings
Conflicts of interest
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call