Abstract
The genetic diversity in Plasmodium falciparum antigens is a major hurdle in developing an effective malaria vaccine. Protective efficacy of the vaccine is dependent on the polymorphic alleles of the vaccine candidate antigens. Therefore, we investigated the genetic diversity of the potential vaccine candidate antigens i.e. msp-1, msp-2, glurp, csp and pfs25 from field isolates of P.falciparum and determined the natural immune response against the synthetic peptide of these antigens. Genotyping was performed using Sanger method and size of alleles, multiplicity of infection, heterogeneity and recombination rate were analyzed. Asexual stage antigens were highly polymorphic with 55 and 50 unique alleles in msp-1 and msp-2 genes, respectively. The MOI for msp-1 and msp-2 were 1.67 and 1.28 respectively. A total 59 genotype was found in glurp gene with 8 types of amino acid repeats in the conserved part of RII repeat region. The number of NANP repeats from 40 to 44 was found among 55% samples in csp gene while pfs25 was found almost conserved with only two amino acid substitution site. The level of genetic diversity in the present study population was very similar to that from Asian countries. A higher IgG response was found in the B-cell epitopes of msp-1 and csp antigens and higher level of antibodies against csp B-cell epitope and glurp antigen were recorded with increasing age groups. Significantly, higher positive responses were observed in the csp antigen among the samples with ≥42 NANP repeats. The present finding showed extensive diversity in the asexual stage antigens.
Highlights
About 3.2 billion people are at risk of malaria and 214 million new malaria cases and 438,000 deaths was reported in 2015[1]
Out of 271, polymerase chain reaction (PCR) positive 180 mono-infected P. falciparam patients who fulfilled the enrolment criteria were included in the study
P. falciparum msp1, msp2 and glurp were highly diverse from central India region in respect of length as well as sequence motifs with prevalence of all the allelic families of msp1 and msp2, which corroborates with earlier reports on Indian isolates [9,10,13,14,31,32]
Summary
About 3.2 billion people are at risk of malaria and 214 million new malaria cases and 438,000 deaths was reported in 2015[1]. South East Asia Region contributed 10% of the global malaria cases, of which India alone accounts for 70% of the cases [1]. Plasmodium falciparum contributes 67% of the total malaria cases in India with a greatly varied proportion from 0% to 93% in different states [2,3]. Malaria is a major health problem in rural/tribal areas of the Central Eastern and North Eastern States of India, which are having large groups of ethnic population [4]. An increasing number of countries including India are in the process of eliminating malaria. In India, despite of scaling up of interventions such as use of insecticides treated net (ITN), indoor residual spray (IRS), improved diagnostic test and treatment using artemisnin combination therapy (ACT), malaria positivity is increasing 0.78% to 0.95% from 2013 to 2015 [2]
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