Vaccine 30 (2012) 767–773 Contents lists available at SciVerse ScienceDirect Vaccine jou rn al h om epa ge: www.elsevier.com/locate/vaccine Antibody response to allelic variants of 19 kDa fragment of MSP-1: Recognition of a variant and protection associated with ethnicity in Assam, India Sonia D. Lourembam, Shashi Baruah ∗ Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam, India a r t i c l e i n f o Article history: Received 2 April 2011 Received in revised form 6 November 2011 Accepted 16 November 2011 Available online 28 November 2011 Keywords: Plasmodium falciparum Antibody response MSP119 variants Whole merozoite extract Assam Ethnicity a b s t r a c t Evidence suggests association of anti MSP-1 19 antibodies with protection from clinical malaria. However, the target epitope was reported to vary with respect to response to conserved or variant epitopes in different studies. We have investigated here humoral response of naturally exposed individuals of Tibeto- Burman and Austro-Asiatic ethnic groups to E-TSR and Q-KNG variants of MSP-1 19 in comparison to whole merozoite extract (WME) of local strain of Plasmodium falciparum in a longitudinal prospective cohort study. The association of antibodies in relation to risk of infection and disease severity was determined. A relatively lower seropositivity to MSP1 19 peptides derived from 3D7 and FVO strains in comparison to whole merozoite extract of local P. falciparum strain was observed. Recognition of Q-KNG variant was markedly lower in TB (p < 0.0001) indicating a role of ethnicity. The Tea tribes of Austro-Asiatic affinity had higher antibody response (E-TSR; p = 0.038 and Q-KNG; p = 0.004) and equally recognized the two variants. A reduced risk of clinical infection in high transmission summer season was seen in presence of anti MSP- 1 19 antibodies (p = 0.013) and antibody level was predictive of risk of clinical malaria (ROC = 0.729). Anti E-TSR antibodies were inversely associated to disease severity at KTE ( 2 p = 0.013; t-test p = 0.032). The present study demonstrated antibody response to MSP-1 19 was associated with protection from frequent episodes of malaria and disease severity and that the host genetic background was important factor in response to MSP-1 19 allelic variant. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Merozoite surface proteins (MSPs) are leading blood stage vac- cine candidate molecules of Plasmodium falciparum. MSP-1 a major surface protein of the parasite, is synthesized as a 190 kDa precur- sor and is proteolytically cleaved to yield four fragments of which only the 19 kDa C-terminal fragment remains anchored on the merozoite surface during erythrocyte invasion [1]. Antibodies tar- geted to this fragment are shown to inhibit erythrocyte invasion by preventing secondary processing that releases this fragment from the rest of the MSP-1 complex [2]. MSP-1 19 fragment is relatively conserved with few single nucleotide polymorphisms (SNPs) iden- tified in its two epidermal growth factor like (EGF-like) domains [3]. At least six SNPs have been reported, one in the first EGF like domain at amino acid position 1644(Q/E) and five in the second EGF like domain corresponding to positions 1691(K/T), 1699(S/N), 1700(N/S), 1701(G/R) and 1716(L/F). Polymorphisms at positions Abbreviations: TB, Tibeto-Burman; TT, Tea tribes; IE, Indo European; KTE, Kon- doli tea estate; WME, whole merozoite extract. ∗ Corresponding author. Tel.: +91 3712 267007/8/9x5408; fax: +91 3712 267006. E-mail addresses: sbaruah@tezu.ernet.in, sashibaruah@gmail.com (S. Baruah). 1691, 1700 and 1701 have been implicated as particularly impor- tant in determining allele specificity of anti MSP-1 19 immunity [4]. Antibodies to MSP-1 19 fragment have been reported to recognize cross reactive as well as allele specific epitopes [5,6]. Further, other investigators observed that certain MSP-1 19 polymorphisms might be more relevant to cross reactive immunity [4]. In context of MSP-1 19 based vaccine molecule, Takala and Plowe [7] emphasized on the need for a polyvalent MSP-1 vaccine that incorporates allelic variants or focuses on residues more relevant to cross protection. Nonetheless, it is important to understand the circulating alleles of MSP-1 and the immune response to them as illustrated by FMP1 vaccine trial in Kenya. Antigen based on C- terminal 42 kDa MSP-1 fragment from 3D7 strain of P. falciparum showed lack of clinical efficacy in phase II pediatric trial conducted in Kenya [8] and the low prevalence of 3D7 allele at this site [9,10] was considered as the reason for failure of the vaccine [7]. Fur- ther, Ferreira et al. [11] reported vaccine induced selective effect resulting in selection for clinical infections with nonvaccine type parasites in vaccinated individuals. Considering the role of natu- ral acquired immunity in antigen polymorphism, it is important to understand the immune responses that confer protection. Assam in northeast India is endemic for malaria. The endemicity of malaria is not uniform with many pockets along forest fringes, 0264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2011.11.069