Limited polymorphism of the vaccine candidate merozoite surface protein 4 of Plasmodium falciparum

Wang, Lina; Marshall, Vikki M.; Coppel, Ross L.

doi:10.1016/s0166-6851(01)00457-1

Cited by 19 publications

(23 citation statements)

References 12 publications

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“…In both cases, they is located in the N-terminal region of the proteins, are due to point mutations, and occur at similar rates (overall, 3.3% for MSP4) (34). Only one amino acid change was identified in the EGF-like domain of MSP4/5 in a single P. yoelii isolate (P. y. nigeriensis N67).…”

Section: Discussionmentioning

confidence: 90%

“…Only one amino acid change was identified in the EGF-like domain of MSP4/5 in a single P. yoelii isolate (P. y. nigeriensis N67). Similarly, only one amino acid change was identified in the EGF-like domain of MSP4 of P. falciparum (34). Cross-reactivity in the antibody response to the recombinant proteins was explored by immunoblotting and ELISA.…”

Section: Discussionmentioning

confidence: 99%

“…The mature protein of msp5 has no reported diversity among the P. falciparum isolates examined (35). Only limited antigenic diversity for MSP4 has been detected, with nine residues exhibiting polymorphism (34). It is not known whether this conservation is due to functional constraints or a lack of immune (or other) selection pressure.…”

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confidence: 99%

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Merozoite Surface Protein 4/5 Provides Protection against Lethal Challenge with a Heterologous Malaria Parasite Strain

Goschnick¹,

Black

Kędzierski³

et al. 2004

Infect Immun

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Merozoite Surface Protein 4/5 Provides Protection against Lethal Challenge with a Heterologous Malaria Parasite Strain

Goschnick¹,

Black

Kędzierski³

et al. 2004

Infect Immun

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“…70, 2002 COMBINED ANTIGENS ENHANCE PROTECTION AGAINST MALARIA 6611 the parasite, such as involvement in alternative invasion pathways. Their small size and relative invariance in sequence makes them attractive candidates for the production by recombinant DNA technology (21,22,40,42). At present we suggest that both proteins (MSP4 and MSP5) should be included and tested in clinical trials in combination with MSP1 19 .…”

Section: Discussionmentioning

confidence: 96%

Immunization with a Combination of Merozoite Surface Proteins 4/5 and 1 Enhances Protection against Lethal Challenge withPlasmodium yoelii

et al. 2002

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It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1 19 combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1 19 and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1 19 were elevated compared to the MSP1 19 alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1 19 response was observed. Boosting of anti-MSP1 19 did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.

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“…Recombinant PfMSP4 protein is immunogenic in laboratory animals and recognized by antibodies from humans living in malaria endemic areas (Wang et al, 1999; 2001). Limited population studies indicate that PfMSP4 has low sequence diversity (Wang et al, 2002, Benet et al, 2004, Polson et al, 2005), and analysis of PvMSP4 sequences from 30 Colombian samples revealed a similar result of limited polymorphisms (Martinez et al, 2005). Yet, it is not clear whether this reflects a recent expansion of similar strains in this region or global conservation of the PvMSP4 locus.…”

Section: Introductionmentioning

confidence: 99%

Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

Putaporntip

Jongwutiwes

Ferreira

et al. 2009

Infection, Genetics and Evolution

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Merozoite surface proteins (MSPs) of the malaria parasites are major candidates for vaccine development targeting asexual blood stages. However, the diverse antigenic repertoire of these antigens that induce strain-specific protective immunity in human is a major challenge for vaccine design and often determines the efficacy of a vaccine. Here we further assessed the genetic diversity of Plasmodium vivax MSP4 (PvMSP4) protein using 195 parasite samples collected mostly from Thailand, Indonesia and Brazil. Overall, PvMSP4 is highly conserved with only eight amino acid substitutions. The majority of the haplotype diversity was restricted to the two short tetrapeptide repeat arrays in exon 1 and 2, respectively. Selection and neutrality tests indicated that exon 1 and the entire coding region of PvMSP4 were under purifying selection. Despite the limited nucleotide polymorphism of PvMSP4, significant genetic differentiation among the three major parasite populations was detected. Moreover, microgeographical heterogeneity was also evident in the parasite populations from different endemic areas of Thailand.

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Limited polymorphism of the vaccine candidate merozoite surface protein 4 of Plasmodium falciparum

Cited by 19 publications

References 12 publications

Merozoite Surface Protein 4/5 Provides Protection against Lethal Challenge with a Heterologous Malaria Parasite Strain

Merozoite Surface Protein 4/5 Provides Protection against Lethal Challenge with a Heterologous Malaria Parasite Strain

Immunization with a Combination of Merozoite Surface Proteins 4/5 and 1 Enhances Protection against Lethal Challenge withPlasmodium yoelii

Limited global diversity of the Plasmodium vivax merozoite surface protein 4 gene

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