Vaccination with recombinant Plasmodium vivax MSP-10 formulated in different adjuvants induces strong immunogenicity but no protection

Giraldo, Manuel A.; Arévalo-Pinzón, Gabriela; Rojas-Caraballo, José; Mongui, Alvaro; Rodríguez, Ricaurte; Patarroyo, Manuel A.

doi:10.1016/j.vaccine.2009.09.046

Cited by 17 publications

(14 citation statements)

References 31 publications

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“…The latter behaviour seems to have been directing pv12 and pv38 evolution, highlighting high conservation at both intra- and inter-species level due to the influence of negative selection exerted on s48/45 domains which are important for red blood cell recognition [30]. Although antigens having low genetic diversity are usually not immunogenic [83] nor do they induce protection-inducing responses [84], some limited polymorphism antigens have been shown to be able to induce immunogenicity and protection [85]. Therefore, pv12 and pv38 (or their s48/45 domains) should be evaluated regarding vaccine development because immune responses against 6-Cys family antigens appear to be directed against structural epitopes in s48/45 domains [86-88], blocking such domains should prevent invasion [30,88] and being highly conserved and having a functional constraint, allele-specific immune responses are thus avoided.…”

Section: Resultsmentioning

confidence: 99%

Low genetic diversity and functional constraint in loci encoding Plasmodium vivax P12 and P38 proteins in the Colombian population

Forero-Rodríguez

Garzón‐Ospina

Patarroyo

2014

Malar J

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BackgroundPlasmodium vivax is one of the five species causing malaria in human beings, affecting around 391 million people annually. The development of an anti-malarial vaccine has been proposed as an alternative for controlling this disease. However, its development has been hampered by allele-specific responses produced by the high genetic diversity shown by some parasite antigens. Evaluating these antigens’ genetic diversity is thus essential when designing a completely effective vaccine.MethodsThe gene sequences of Plasmodium vivax p12 (pv12) and p38 (pv38), obtained from field isolates in Colombia, were used for evaluating haplotype polymorphism and distribution by population genetics analysis. The evolutionary forces generating the variation pattern so observed were also determined.ResultsBoth pv12 and pv38 were shown to have low genetic diversity. The neutral model for pv12 could not be discarded, whilst polymorphism in pv38 was maintained by balanced selection restricted to the gene’s 5′ region. Both encoded proteins seemed to have functional/structural constraints due to the presence of s48/45 domains, which were seen to be highly conserved.ConclusionsDue to the role that malaria parasite P12 and P38 proteins seem to play during invasion in Plasmodium species, added to the Pv12 and Pv38 antigenic characteristics and the low genetic diversity observed, these proteins might be good candidates to be evaluated in the design of a multistage/multi-antigen vaccine.

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Section: Resultsmentioning

confidence: 99%

Low genetic diversity and functional constraint in loci encoding Plasmodium vivax P12 and P38 proteins in the Colombian population

Forero-Rodríguez

Garzón‐Ospina

Patarroyo

2014

Malar J

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“…vivax populations. Though conserved regions in malaria antigens are generally not highly immunogenic and protective [ 72 , 73 ], antibodies against block II have been significantly associated with protection against clinical P . vivax infections [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Evolution of PvMSP3α Block II in Plasmodium vivax from Diverse Geographic Origins

Gupta

Reddy

Fan³

et al. 2015

PLoS ONE

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Block II of Plasmodium vivax merozoite surface protein 3α (PvMSP3α) is conserved and has been proposed as a potential candidate for a malaria vaccine. The present study aimed to compare sequence diversity in PvMSP3a block II at a local microgeographic scale in a village as well as from larger geographic regions (countries and worldwide). Blood samples were collected from asymptomatic carriers of P. vivax in a village at the western border of Thailand and PvMSP3α was amplified and sequenced. For population genetic analysis, 237 PvMSP3α block II sequences from eleven P. vivax endemic countries were analyzed. PvMSP3α sequences from 20 village-level samples revealed two length variant types with one type containing a large deletion in block I. In contrast, block II was relatively conserved; especially, some non-synonymous mutations were extensively shared among 11 parasite populations. However, the majority of the low-frequency synonymous variations were population specific. The conserved pattern of nucleotide diversity in block II sequences was probably due to functional/structural constraints, which were further supported by the tests of neutrality. Notably, a small region in block II that encodes a predicted B cell epitope was highly polymorphic and showed signs of balancing selection, signifying that this region might be influenced by the immune selection and may serve as a starting point for designing multi-antigen/stage epitope based vaccines against this parasite.

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“…Whereas very little is known about the immunogenicity and protection efficacy of MSP10 as a vaccine, there is evidence that shows strong immunogenicity, but no protection in immunized Aotus monkeys with a recombinant P. vivax MSP10 (Giraldo et al, 2010). Given that both MSP8 and MSP10 share structural features with proteins from the MSP family, especially with MSP1 (Black et al, 2003, Puentes et al, 2005,) and based on the highly conserved nature of their EGF-like domain across different species of Plasmodium , we suggest that not only MSP8, but also MSP10 should be explored in further development of chimeric vaccines with MSP1.…”

Section: Discussionmentioning

confidence: 99%

Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp.

Pacheco

Elango

Rahman

et al. 2012

Infection, Genetics and Evolution

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Evidence for natural selection, positive or negative, on gene encoding antigens may indicate variation or functional constraints that are immunologically relevant. Most malaria surface antigens with high genetic diversity have been reported to be under positive-diversifying selection. However, antigens with limited genetic variation are usually ignored in terms of the role that natural selection may have in generating such patterns. We investigated orthologous genes encoding two merozoite proteins, MSP8 and MSP10, among several mammalian Plasmodium spp. These antigens, together with MSP1, are among the few MSPs that have two epidermal growth factor-like domains (EGF) at the C-terminal. Those EGF are relatively conserved (low levels of genetic polymorphism) and have been proposed to act as ligands during the invasion of RBCs. We use several evolutionary genetic methods to detect patterns consistent with natural selection acting on MSP8 and MSP10 orthologs in the human parasites P. falciparum and P. vivax, as well as closely related malarial species found in non-human primates (NHPs). Overall, these antigens have low polymorphism in the human parasites in comparison with the orthologs from other Plasmodium species. We found that the MSP10 gene polymorphism in P. falciparum only harbor non-synonymous substitutions, a pattern consistent with a gene under positive selection. Evidence of purifying selection was found on the polymorphism observed in both orthologs from P. cynomolgi, a non-human primate parasite closely related to P. vivax, but it was not conclusive in the human parasite. Yet, using phylogenetic base approaches, we found evidence for purifying selection on both MSP8 and MSP10 in the lineage leading to P. vivax. Such antigens evolving under strong functional constraints could become valuable vaccine candidates. We discuss how comparative approaches could allow detecting patterns consistent with negative selection even when there is low polymorphism in the extant populations.

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Vaccination with recombinant Plasmodium vivax MSP-10 formulated in different adjuvants induces strong immunogenicity but no protection

Cited by 17 publications

References 31 publications

Low genetic diversity and functional constraint in loci encoding Plasmodium vivax P12 and P38 proteins in the Colombian population

Low genetic diversity and functional constraint in loci encoding Plasmodium vivax P12 and P38 proteins in the Colombian population

Molecular Evolution of PvMSP3α Block II in Plasmodium vivax from Diverse Geographic Origins

Evidence of purifying selection on merozoite surface protein 8 (MSP8) and 10 (MSP10) in Plasmodium spp.

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