Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali.

Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Research Abstract Details 

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Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Abstract Text:

BACKGROUND: Malaria vaccines based on the 19-kDa region of merozoite surface protein 1 (MSP-1(19)) derived from the 3D7 strain of Plasmodium falciparum are being tested in clinical trials in Africa. Knowledge of the distribution and natural dynamics of vaccine antigen polymorphisms in populations in which malaria vaccines will be tested will guide vaccine design and permit distinction between natural fluctuations in genetic diversity and vaccine-induced selection. METHODS AND FINDINGS: Using pyrosequencing, six single-nucleotide polymorphisms in the nucleotide sequence encoding MSP-1(19) were genotyped from 1,363 malaria infections experienced by 100 children who participated in a prospective cohort study in Mali from 1999 to 2001. The frequencies of 14 MSP-1(19) haplotypes were compared over the course of the malaria transmission season for all three years, in three age groups, and in consecutive infections within individuals. While the frequency of individual MSP-1(19) haplotypes fluctuated, haplotypes corresponding to FVO and FUP strains of P. falciparum (MSP-1(19) haplotypes QKSNGL and EKSNGL, respectively) were most prevalent during three consecutive years and in all age groups with overall prevalences of 46% (95% confidence interval [CI] 44%-49%) and 36% (95% CI 34%-39%), respectively. The 3D7 haplotype had a lower overall prevalence of 16% (95% CI 14%-18%). Multiplicity of infection based on MSP-1(19) was higher at the beginning of the transmission season and in the oldest individuals (aged > or =11 y). Three MSP-1(19) haplotypes had a reduced frequency in symptomatic infections compared to asymptomatic infections. Analyses of the dynamics of MSP-1(19) polymorphisms in consecutive infections implicate three polymorphisms (at positions 1691, 1700, and 1701) as being particularly important in determining allele specificity of anti-MSP-1(19) immunity. CONCLUSIONS: Parasites with MSP-1(19) haplotypes different from that of the leading vaccine strain were consistently the most prevalent at a vaccine trial site. If immunity elicited by an MSP-1-based vaccine is allele-specific, a vaccine based on either the FVO or FUP strain might have better initial efficacy at this site. This study, to our knowledge the largest of its kind to date, provides molecular information needed to interpret population responses to MSP-1-based vaccines and suggests that certain MSP-1(19) polymorphisms may be relevant to cross-protective immunity.

Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Publishing Authors By Initials

For similar genetic processes: selection (genetics) research abstracts see: genetic processes: selection (genetics) research

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Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: PLoS medicine

VOLUME: 4

Page Numbers: e93

Journal Abbreviation: PLoS Med.

ISSN: 1549-1676

DAY: 3

MONTH: Mar

YEAR: 2007

Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101231360

Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Keywords Mesh Terms:

KEYWORDS: Selection (Genetics)

MESH TERMS: genetics

Chemical & Substance for Abstract: Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. Information

Substance Name: Protozoan Proteins

Registry Number: 0

Grant and Affiliation Information for Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali.

AFFILIATION: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Country: United States

AGENCY: United States NIAID

GRANT: U19AI065683

ACRONYM: AI

MEDLINETA: PLoS Med

REFSOURCE: PLoS Med. 2007 Mar;4(3):e116

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