Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection.

Abstract

BACKGROUND:

Plasmodium falciparum merozoite surface protein (MSP) 3 is an asexual blood-stage malaria vaccine candidate antigen. Sequence polymorphisms divide alleles into 2 major types, but the adaptive and immunological significance of the types has not been defined.

METHODS:

One hundred one msp3 allele sequences were sampled from 2 populations living in areas where malaria is endemic and were analyzed for evidence of natural selection. Recombinant antigens representing full-length sequences of different allelic types and a relatively conserved C-terminal region were produced, to evaluate immunization-induced antibody responses in mice and protective associations for naturally acquired antibodies in a cohort of 319 Gambian children under surveillance for malaria.

RESULTS:

Frequency-based statistical analyses indicated that polymorphisms are maintained by balancing selection in each of the 2 populations studied. Immunization of mice with full-length MSP3 antigens induced predominantly type-specific antibodies, and a large proportion of naturally acquired antibodies to MSP3 in humans also discriminated between the alleles. Among Gambian children, antibodies to allele-specific and conserved epitopes in MSP3 were associated prospectively with protection from clinical malaria, even after adjustment for age and for the presence of antibodies to other merozoite antigens.

CONCLUSIONS:

A vaccine incorporating both major allelic types of this promising candidate antigen could be particularly useful for induction of protective immunity in infants and young children.

• Authors: Spencer D Polley, Kevin K A Tetteh, Jennie M Lloyd, Onome J Akpogheneta, Brian M Greenwood, Kalifa A Bojang, David J Conway
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 195 Issue 2 Pg. 279-87 (Jan 15 2007) ISSN: 0022-1899 [Print] United States
• PMID: 17191173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Malaria Vaccines
• Protozoan Proteins
• Recombinant Proteins
• merozoite surface protein 3, Plasmodium

Topics

• Alleles
• Animals
• Antibodies, Protozoan (blood, immunology)
• Antibody Specificity
• Antigens, Protozoan (genetics, immunology, metabolism)
• Child
• Child, Preschool
• Gambia
• Humans
• Immunization
• Malaria Vaccines (administration & dosage, genetics, immunology)
• Malaria, Falciparum (immunology, prevention & control)
• Mice
• Molecular Sequence Data
• Nigeria
• Plasmodium falciparum (genetics, immunology, metabolism)
• Protozoan Proteins (genetics, immunology, metabolism)
• Recombinant Proteins (genetics, immunology, metabolism)
• Selection, Genetic
• Sequence Analysis, DNA
• Thailand