Development of a bivalent conjugate vaccine candidate against malaria transmission and typhoid fever |
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| Affiliation: | 1. Laboratory of Malaria Immunology and Vaccinology, Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA;2. International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, 151-742 Seoul, Republic of Korea;1. Department of Medicine, Dalhousie University, QEII Health Sciences Centre, VG Site, Suite 442 Bethune Building, 1276 South Park Street, Halifax, NS B3H 2Y9, Canada;2. The Division of Diagnostic and Applied Microbiology, Department of Laboratory Medicine and Pathology, University of Alberta, and The Provincial Laboratory for Public Health, 8440 112 St, Edmonton, Alberta T6G 2J2, Canada;3. Department of Medicine, Faculty of Medicine & Dentistry, 2J2.00 Walter C Mackenzie Health Sciences Centre, 8440 112 St. NW, Edmonton, Alberta T6G 2R7, Canada;4. School of Public Health, University of Alberta, 2-040 Li Ka Shing HRIF, Edmonton, AB, T6G 2E1, Canada;1. CEREB – Center of Empirical Research in Economics and Behavioral Sciences, Media and Communication Science, University of Erfurt, Nordhäuser Str. 63, 99089 Erfurt, Germany;2. Immunization Unit, Robert Koch Institute, Seestraße 10, 13353 Berlin, Germany;3. Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;1. National Immunization Program, Chinese Center for Disease Control and Prevention, No. 27, Nanwei Road, Xicheng District, Beijing, China;2. National Health and Family Planning Commission of the People''s Republic of China, No. 1, Xizhimenwai Street, Xicheng District, Beijing, China;3. World Health Organization Office in China, 401, Dongwai Diplomatic Office Building, No. 23, Dong zhi men wai Street, Beijing, China |
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| Abstract: | Immune responses to poorly immunogenic antigens, such as polysaccharides, can be enhanced by conjugation to carriers. Our previous studies indicate that conjugation to Vi polysaccharide of Salmonella Typhi may also enhance immunogenicity of some protein carriers. We therefore explored the possibility of generating a bivalent vaccine against Plasmodium falciparum malaria and typhoid fever, which are co-endemic in many parts of the world, by conjugating Vi polysaccharide, an approved antigen in typhoid vaccine, to Pfs25, a malaria transmission blocking vaccine antigen in clinical trials. Vi-Pfs25 conjugates induced strong immune responses against both Vi and Pfs25 in mice, whereas the unconjugated antigens are poorly immunogenic. Functional assays of immune sera revealed potent transmission blocking activity mediated by anti-Pfs25 antibody and serum bactericidal activity due to anti-Vi antibody. Pfs25 conjugation to Vi modified the IgG isotype distribution of antisera, inducing a Th2 polarized immune response against Vi antigen. This conjugate may be further developed as a bivalent vaccine to concurrently target malaria and typhoid fever. |
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| Keywords: | Malaria Pfs25 Transmission blocking vaccine Vi capsular polysaccharide Typhoid fever Conjugate vaccine |
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