Evaluation of the genetic polymorphism of Plasmodium falciparum P126 protein (SERA or SERP) and its influence on naturally acquired specific antibody responses in malaria-infected individuals living in the Brazilian Amazon.
BACKGROUND
The Plasmodium falciparum P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth in vitro, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain--OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in P. falciparum isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies.


METHODS
The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain.


RESULTS
Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response.


CONCLUSIONS
These findings confirm a limited genetic polymorphism of the P126 OR domain in P. falciparum isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.
Pratt-Riccio
Lilian Rose
LR
Laboratório de Pesquisas em Malária, Departamento de Imunologia, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, Brazil.
Sallenave-Sales
Selma
S
de Oliveira-Ferreira
Joseli
J
da Silva
Bruno T
BT
Guimarães
Monick Lindenmeyer
ML
Santos
Fátima
F
de Simone
Thatiane S
TS
Morgado
Mariza G
MG
de Simone
Salvatore G
SG
Ferreira-Da-Cruz
Maria de Fátima
Mde F
Daniel-Ribeiro
Cláudio T
CT
Zalis
Mariano G
MG
Camus
Daniel
D
Banic
Dalma M
DM
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001938:Brazil; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D017422:Sequence Analysis, DNA
D000913:Antibodies, Protozoan; C085732:P126 protein, Plasmodium falciparum; D015800:Protozoan Proteins