Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2

Bankala Krishnarjuna, Dean Andrew, Christopher A MacRaild, Rodrigo A V Morales, James G Beeson, Robin F Anders, Jack S Richards, Raymond S Norton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

MSP2 is an intrinsically disordered protein that is abundant on the merozoite surface and essential to the parasite Plasmodium falciparum. Naturally-acquired antibody responses to MSP2 are biased towards dimorphic sequences within the central variable region of MSP2 and have been linked to naturally-acquired protection from malaria. In a phase IIb study, an MSP2-containing vaccine induced an immune response that reduced parasitemias in a strain-specific manner. A subsequent phase I study of a vaccine that contained both dimorphic forms of MSP2 induced antibodies that exhibited functional activity in vitro. We have assessed the contribution of the conserved and variable regions of MSP2 to the generation of a strain-transcending antibody response by generating MSP2 chimeras that included conserved and variable regions of the 3D7 and FC27 alleles. Robust anti-MSP2 antibody responses targeting both conserved and variable regions were generated in mice, although the fine specificity and the balance of responses to these regions differed amongst the constructs tested. We observed significant differences in antibody subclass distribution in the responses to these chimeras. Our results suggest that chimeric MSP2 antigens can elicit a broad immune response suitable for protection against different strains of P. falciparum.

Original languageEnglish
Article number20613
Number of pages12
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 11 Feb 2016

Cite this

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title = "Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2",
abstract = "MSP2 is an intrinsically disordered protein that is abundant on the merozoite surface and essential to the parasite Plasmodium falciparum. Naturally-acquired antibody responses to MSP2 are biased towards dimorphic sequences within the central variable region of MSP2 and have been linked to naturally-acquired protection from malaria. In a phase IIb study, an MSP2-containing vaccine induced an immune response that reduced parasitemias in a strain-specific manner. A subsequent phase I study of a vaccine that contained both dimorphic forms of MSP2 induced antibodies that exhibited functional activity in vitro. We have assessed the contribution of the conserved and variable regions of MSP2 to the generation of a strain-transcending antibody response by generating MSP2 chimeras that included conserved and variable regions of the 3D7 and FC27 alleles. Robust anti-MSP2 antibody responses targeting both conserved and variable regions were generated in mice, although the fine specificity and the balance of responses to these regions differed amongst the constructs tested. We observed significant differences in antibody subclass distribution in the responses to these chimeras. Our results suggest that chimeric MSP2 antigens can elicit a broad immune response suitable for protection against different strains of P. falciparum.",
author = "Bankala Krishnarjuna and Dean Andrew and MacRaild, {Christopher A} and Morales, {Rodrigo A V} and Beeson, {James G} and Anders, {Robin F} and Richards, {Jack S} and Norton, {Raymond S}",
year = "2016",
month = "2",
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doi = "10.1038/srep20613",
language = "English",
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journal = "Scientific Reports",
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Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2. / Krishnarjuna, Bankala; Andrew, Dean; MacRaild, Christopher A; Morales, Rodrigo A V; Beeson, James G; Anders, Robin F; Richards, Jack S; Norton, Raymond S.

In: Scientific Reports, Vol. 6, 20613, 11.02.2016.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Andrew, Dean

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AU - Beeson, James G

AU - Anders, Robin F

AU - Richards, Jack S

AU - Norton, Raymond S

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