Molecular basis of allele-specific efficacy of a blood-stage malaria vaccine: vaccine development implications.
J Infect Dis
; 207(3): 511-9, 2013 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-23204168
The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on blood-stage antigens. FMP2.1/AS02(A), a blood-stage candidate vaccine based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, had allele-specific efficacy against clinical malaria in a phase II trial in Malian children. We assessed the cross-protective efficacy of the malaria vaccine and inferred which polymorphic amino acid positions in AMA1 were the targets of protective allele-specific immune responses. FMP2.1/AS02(A) had the highest efficacy against AMA1 alleles that were identical to the 3D7 vaccine-type allele at 8 highly polymorphic amino acid positions in the cluster 1 loop (c1L) but differed from 3D7 elsewhere in the molecule. Comparison of the incidence of vaccine-type alleles before and after vaccination in the malaria vaccine and control groups and examination of the patterns of allele change at polymorphic positions in consecutive malaria episodes suggest that the highly polymorphic amino acid position 197 in c1L was the most critical determinant of allele-specific efficacy. These results indicate that a multivalent AMA1 vaccine with broad efficacy could include only a limited set of key alleles of this extremely polymorphic antigen.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Proteínas Protozoarias
/
Malaria Falciparum
/
Vacunas contra la Malaria
/
Alelos
/
Proteínas de la Membrana
/
Antígenos de Protozoos
Tipo de estudio:
Clinical_trials
Límite:
Child
/
Child, preschool
/
Humans
/
Infant
Idioma:
En
Revista:
J Infect Dis
Año:
2013
Tipo del documento:
Article
País de afiliación:
Mali
Pais de publicación:
Estados Unidos