Abstract
Circumsporozoite protein (CSP) is the primary pre-erythrocytic vaccine target in Plasmodium species. Knowledge about their genetic diversity can help predict vaccine efficacy and the spread of novel parasite variants. Thus, we investigated pvcsp gene polymorphisms in 219 isolates (136 from Brazilian Amazon [BA], 71 from Rio de Janeiro Atlantic Forest [AF], and 12 from non-Brazilian countries [NB]). Forty-eight polymorphic sites were detected, 46 in the central repeat region (CR), and two in the C-terminal region. Also, the CR presents InDels and a variable number of repeats. All samples correspond to the VK210 variant, and 24 VK210 subtypes based on CR. Nucleotide diversity (π = 0.0135) generated a significant number of haplotypes (168) with low genetic differentiation between the Brazilian regions (Fst = 0.208). The haplotype network revealed similar distances among the BA and AF regions. The linkage disequilibrium indicates that recombination does not seem to be acting in diversity, reinforcing natural selection’s role in accelerating adaptive evolution. The high diversity (low Fst) and polymorphism frequencies could be indicators of balancing selection. Although malaria in BA and AF have distinct vector species and different host immune pressures, consistent genetic signature was found in two regions. The immunodominant B-cell epitope mapped in the CR varies from seven to 19 repeats. The CR T-cell epitope is conserved only in 39 samples. Concerning to C-terminal region, the Th2R epitope presented nonsynonymous SNP only in 6% of Brazilian samples, and the Th3R epitope remained conserved in all studied regions. We conclude that, although the uneven distribution of alleles may jeopardize the deployment of vaccines directed to a specific variable locus, a unique vaccine formulation could protect populations in all Brazilian regions.
Highlights
Malaria is the most prevalent infectious disease globally, with an estimated 228 million cases and 405 thousand deaths in 2018 [1]
Plasmodium falciparum is responsible for most cases and deaths from malaria, P. vivax is by far the most widespread, accounting for almost half of non-African malaria cases [2]
Malaria cases have substantially decreased in Southeast Brazil after the malaria eradication campaign in 1960 [4], residual P. vivax cases persist in Atlantic Forest (AF) areas until today, probably as a zoonotic transmission [6]
Summary
Malaria is the most prevalent infectious disease globally, with an estimated 228 million cases and 405 thousand deaths in 2018 [1]. Plasmodium falciparum is responsible for most cases and deaths from malaria, P. vivax is by far the most widespread, accounting for almost half of non-African malaria cases [2]. Malaria cases have substantially decreased in Southeast Brazil after the malaria eradication campaign in 1960 [4], residual P. vivax cases persist in AF areas until today, probably as a zoonotic transmission [6]. The An. cruzii, known for its acrodendrophilic habit, bites monkeys in the canopy and, eventually, humans at ground level. This mosquito behavior makes possible zoonotic malaria transmission in Southeastern Brazil, where monkeys are the parasite reservoir [7,8,9]. Genetic and morphological similarities between P. vivax, which infects humans, and P. simium, which infects monkeys in the Atlantic Forest, is consistent with host switches between them in recent evolutionary times [6, 10,11,12]
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