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The current status of typhoid vaccine development and clinical trials with typhoid vaccines
M M Levine1, C O Tacket, D Herrington
1Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Abstract:
The killed whole cell typhoid vaccines, although protective, have limited usefulness because of the adverse reactions they evoke. In contrast, new typhoid vaccines protect without reactogenicity. Attenuated oral vaccine Ty2la has been evaluated in field trials of efficacy in Santiago, Chile. Three doses of Ty2la in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Ty2la has reached the stage of being a practical public health tool. Two double auxotrophic (Aro-, Pur-) mutant strains of S. typhi (541Ty and 543Ty) were well-tolerated and stimulated cell-mediated immune responses but evoked little serological response. Parenteral purified Vi polysaccharide of S. typhi (single 25 mcg dose) was safe and immunogenic and provided 64-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.
Insights
New typhoid vaccines offer protection without adverse reactions. Oral Ty2la vaccine showed 69% efficacy for four years, becoming a public health tool, while Vi polysaccharide vaccines also demonstrated significant protection.
Area of Science:
- Vaccinology and Infectious Diseases
- Microbiology and Immunology
- Public Health and Epidemiology
Background:
- Traditional killed whole cell typhoid vaccines induce protection but cause adverse reactions, limiting their clinical utility.
- Development of novel typhoid vaccines aims to achieve protection with reduced or eliminated reactogenicity.
Purpose of the Study:
- To evaluate the efficacy and safety of new typhoid vaccine candidates, including attenuated oral Ty2la and parenteral Vi polysaccharide.
- To assess the potential of these vaccines as practical public health tools for typhoid fever prevention.
Main Methods:
- Field trials were conducted to assess the efficacy of the attenuated oral Ty2la vaccine (three doses, enteric-coated) in Santiago, Chile.
- Safety and immunogenicity of double auxotrophic mutant strains (541Ty, 543Ty) of Salmonella Typhi were evaluated.
- Controlled field trials assessed the efficacy of a parenteral purified Vi polysaccharide vaccine (single 25 mcg dose) in Nepal and South Africa.
Main Results:
- The oral Ty2la vaccine demonstrated 69% efficacy for at least four years.
- Double auxotrophic mutant strains were well-tolerated, stimulating cell-mediated immunity with minimal serological response.
- The Vi polysaccharide vaccine was safe, immunogenic, and provided 64-72% protection for 17-21 months.
Conclusions:
- The attenuated oral Ty2la vaccine represents a significant advancement, proving effective and suitable for public health implementation.
- Parenteral Vi polysaccharide vaccine offers a safe and effective alternative for typhoid fever prevention.
- These novel typhoid vaccines overcome the limitations of older vaccines, offering improved safety and sustained protection.