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Comparison of immunogenicity of five MSP1-based malaria vaccine candidate antigens in rabbits
Authors:Zarifah Hussain Reed  Marie Paule Kieny  Howard Engers  Martin Friede  Sandra Chang  Shirley Longacre  Pawan Malhotra  Weiqing Pan  Carole Long
Affiliation:1. Initiative for Vaccines Research, World Health Organization, Geneva, Switzerland;2. Special Programme for Research and Training in Tropical Diseases (TDR),World Health Organization, Geneva, Switzerland;3. Department of Tropical Medicine and Medical Microbiology & Pharmacology, John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA;4. Laboratoire de Vaccinologie Parasitaire, Institut Pasteur, Paris, France;5. International Centre for Genetic Engineering and Biotechnology, New Delhi, India;6. Second Military Medical University, Shanghai, China;g Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Abstract:A number of laboratories around the world are producing Plasmodium falciparum erythrocyte-stage vaccine candidates in the pursuit of a vaccine against clinical malaria disease. These candidates are often based on the same parasite protein. Rigorous clinical development and testing of multiple candidates is limited by available resources, which underscores the need to conduct comparative studies of the different vaccine candidates. The purpose of this study was to compare five different candidate proteins all based on P. falciparum merozoite surface protein-1 (MSP1). After investigators submitted their candidates, basic protein profiles were evaluated in a blinded fashion by an independent laboratory, and groups of rabbits were immunized with the proteins. Sera obtained from the rabbits were compared for antibody titers by ELISA and for functional activity by an in vitro parasite growth inhibition assay (GIA) activity, again in a blinded fashion. In selected cases the fine specificity of the antibodies was assessed. Significant differences in immunogenicity as well as the functional activity of antibodies induced by the various vaccine candidates were noted. Data from this study can assist in making decisions for further clinical development of MSP1-based candidates, and this process sets a precedent for future comparisons of malaria vaccine candidates.
Keywords:MSP1, merozoite surface protein-1   AMA-1, apical membrane antigen-1   PfCP-2.9, P. falciparum chimeric protein 2.9   IFA, immunofluorescence assay   EGF, epidermal growth factor   mcs, multiple cloning site   GIA, growth inhibition assay
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