Background
There is an intense global effort to develop an effective vaccine in addition to the malaria control measures currently in use. Several vaccine candidate antigens have been identified against different stages of the two main human malaria parasites,
Plasmodium falciparum and
Plasmodium vivax, and are being developed as a part of a subunit vaccine [
1,
2]. One of the major concerns in malaria vaccine development is the polymorphic nature of the candidate vaccine antigens. Several
in vitro and epidemiological studies have demonstrated that natural variations can abrogate immune recognition [
3,
4]. Thus, studies of sequence and antigenic diversity of malaria vaccine candidate antigens become a subject of considerable importance.
The merozoite surface protein 1 (MSP-1) of
Plasmodium sp. is a large polypeptide of ~200 kDa and is one of the leading asexual blood stage vaccine candidate antigens [
5]. A number of experimental studies with native and recombinant MSP-1, particularly its C-terminal fragments, have demonstrated the vaccine potential of MSP-1 [
6,
7]. Polymorphism has been reported in the
P. falciparum MSP-1 (
Pfmsp-1) gene among different isolates across different geographical areas [
3]. Based on sequence variations, the
Pfmsp-1 gene has been divided into a number of blocks that are conserved, semi-conserved and variable in different species and isolates [
5]. Broadly,
Pfmsp-1 gene sequences have been classified into two allelic families, Wellcome and PNG-MAD 20 type [
5,
8]. In addition, intragenic recombinations have been reported among these two parental alleles, resulting in polymorphism among different isolates around the world [
9,
10].
The gene encoding the merozoite surface protein 1 of
P. vivax (
Pvmsp-1) shows many similarities with those from other malaria species. The gene consists of 10 relatively conserved blocks alternating with regions of high diversity [
5]. Like the
Pfmsp-1 gene, the
Pvmsp-1 gene has also been shown to be dimorphic; identified as Belem, type 1 [
11] and Salvador-1, type 2 [
12] forms. In comparison to
Pfmsp-1 polymorphism studies, studies on
Pvmsp-1 polymorphism are limited. Several regions of
Pvmsp-1 have been amplified and sequenced from field isolates collected from Sri Lanka, Colombia, Brazil, Thailand, Korea and China [
13‐
18]. A third allele type (type 3) has been reported among these isolates and it has been suggested that this allele has arisen due to intragenic recombination between the Belem and Salvador alleles [
18,
19]. Recently, a detailed study of
P. vivax merozoite surface protein 1 (
Pvmsp-1) gene of 40 isolates from different geographical areas (Thailand, Brazil, Bangladesh, South Korea, Vanuatu and Japan) revealed mosaic organization of the
Pvmsp-1 gene and heterogeneity in the frequency of allelic recombination among different isolates [
16].
The genetic characteristics of
P. vivax circulating in distant endemic regions have not been studied so far. Therefore, the molecular basis underlying phenomena such as resistance of
P. vivax to chloroquine in America and Asia (20,21) and effective immune responses (which is essential for vaccine design), have not being fully understood. Since PvMSP-1 is a potential vaccine candidate for
P. vivax, it is important to further analyse the extent of polymorphism from field isolates across the globe. In the present study, the extent of polymorphism in one of the variable regions of
Pvmsp-1 gene among Indian and Colombian isolates was investigated. This study is important as there is no information of
Pvmsp-1 alleles and their diversity among Indian isolates in spite of
P. vivax being one of the major causes of malaria in India [
22].
Acknowledgements
We thank Dr. S.M.A. Abidi of Section of Parasitology, Department of Zoology, Aligarh Muslim University, Aligarh for his help in collecting Plasmodium-infected blood from that region. We thank Kavitha for assistance in DNA preparation. Collection and processing of the samples in Colombia was funded by Instituto Colombiano de Medicina Tropical, Universidad de Antioquia and COLCIENCIAS Código 3256-04-1041-98, CT-07899.
Authors' contributions
MA was involved in amplification of the samples. SS was involved in amplification, sequencing of the samples and preparation of the manuscript. Both MA and SS contributed equally. GA participated in sample collection in India. AM was involved in sample collection and sequence alignment. EM, CM and BS were involved in sample collection from Colombia. VSC, the group leader participated in the design and co-ordination of the study. PM supervised the overall work.