Antigenic Polymorphism and Naturally Acquired Antibodies to Plasmodium vivax Merozoite Surface Protein 1 in Rural Amazonians
- 1 October 2007
- journal article
- research article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 14 (10), 1249-1259
- https://doi.org/10.1128/cvi.00243-07
Abstract
Merozoite surface protein 1 of Plasmodium vivax (PvMSP-1), a major target for malaria vaccine development, contains six highly polymorphic domains interspersed with conserved sequences. Although there is evidence that the sequence divergence in PvMSP-1 has been maintained over 5 million years by balanced selection exerted by the host's acquired immunity, the variant specificity of naturally acquired antibodies to PvMSP-1 remains poorly investigated. Here, we show that 15 recombinant proteins corresponding to PvMSP-1 variants commonly found in local parasites were poorly recognized by 376 noninfected subjects aged 5 to 90 years exposed to malaria in rural Amazonia; less than one-third of them had detectable immunoglobulin G (IgG) antibodies to at least one variant of blocks 2, 6, and 10 that were expressed, although 54.3% recognized the invariant 19-kDa C-terminal domain PvMSP-1 19 . Although the proportion of responders to PvMSP-1 variants increased substantially during subsequent acute P. vivax infections, the specificity of IgG antibodies did not necessarily match the PvMSP-1 variant(s) found in infecting parasites. We discuss the relative contribution of antigenic polymorphism, poor immunogenicity, and original antigenic sin (the skew in the specificity of antibodies elicited by exposure to new antigenic variants due to preexisting variant-specific responses) to the observed patterns of antibody recognition of PvMSP-1. We suggest that antibody responses to the repertoire of variable domains of PvMSP-1 to which subjects are continuously exposed are elicited only after several repeated infections and may require frequent boosting, with clear implications for the development of PvMSP-1-based subunit vaccines.Keywords
This publication has 36 references indexed in Scilit:
- Population Structure and Transmission Dynamics ofPlasmodium vivaxin Rural AmazoniaThe Journal of Infectious Diseases, 2007
- Mapping the global extent of malaria in 2005Trends in Parasitology, 2006
- A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1Infection and Immunity, 2006
- Antigenic Diversity and Immune Evasion by Malaria ParasitesClinical and Vaccine Immunology, 2004
- Controle da malária no Brasil: 1965 a 2001Revista Panamericana de Salud Pública, 2002
- Wide distribution of Plasmodium ovale in MyanmarTropical Medicine & International Health, 2002
- Natural selection on polymorphic malaria antigens and the search for a vaccineParasitology Today, 1997
- Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprintingInternational Immunology, 1996
- Human immune response to MSP-1Parasitology Today, 1996
- Parasite features impeding malaria immunity: antigen diversity, antigenic variation and poor immunogenicityResearch in Immunology, 1991