Enhanced protection against malaria by a chimeric merozoite surface protein vaccine.

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Research Abstract Details 

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Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Abstract Text:

Qifang Shi,Michelle M Lynch,Margarita Romero,James M Burns,

The 42-kDa processed fragment of Plasmodium falciparum merozoite surface protein 1 (MSP-1(42)) is a prime candidate for a blood-stage malaria vaccine. Merozoite surface protein 8 contains two C-terminal epidermal growth factor (EGF)-like domains that may function similarly to those of MSP-1(42). Immunization with either MSP-1 or MSP-8 induces protection that is mediated primarily by antibodies against conformation-dependent epitopes. In a series of comparative immunogenicity and efficacy studies using the Plasmodium yoelii rodent model, we tested the ability of recombinant P. yoelii MSP-8 (rPyMSP-8) to complement rPyMSP-1-based vaccines. Unlike MSP-1, PyMSP-8-dependent protection required immunization with the full-length protein and was not induced with recombinant antigens that contained only the C-terminal EGF-like domains. Unlike PyMSP-8, the immunogenicity of the PyMSP-1 EGF-like domains was low when present as part of the rPyMSP-1(42) antigen. Immunization with a mixture of rPyMSP-1(42) and rPyMSP-8 further inhibited the antibody response to protective epitopes of rPyMSP-1(42) and did not improve vaccine efficacy. To improve PyMSP-1 immunogenicity, we produced a chimeric antigen containing the EGF-like domains of PyMSP-1 fused to the N terminus of PyMSP-8. Immunization with the chimeric rPyMSP-1/8 antigen induced high and comparable antibody responses against the EGF-like domains of both PyMSP-1 and PyMSP-8. This enhanced MSP-1-specific antibody response and the concurrent targeting of MSP-1 and MSP-8 resulted in improved, nearly complete protection against lethal P. yoelii 17XL malaria. Unexpectedly, immunization with rPyMSP-1/8 failed to protect against challenge infection with reticulocyte-restricted P. yoelii 17X parasites. Overall, these data establish an effective strategy to improve the efficacy of P. falciparum MSP-based vaccines.

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Publishing Authors By Initials

Q Shi,MM Lynch,M Romero,JM Burns,

For similar complex mixtures: biological products: vaccines: vaccines, subunit research abstracts see: complex mixtures: biological products: vaccines: vaccines, subunit research

PUBMED ID PMID:

MEDLINE DATE:

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Infection and immunity

VOLUME: 75

Page Numbers: 1349-58

Journal Abbreviation: Infect. Immun.

ISSN: 0019-9567

DAY: 11

MONTH: 12

YEAR: 2006

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 246127

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Keywords Mesh Terms:

KEYWORDS: Vaccines, Subunit

MESH TERMS: immunology

Chemical & Substance for Abstract: Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Information

Substance Name: merozoite surface protein 8, Plasmodium

Registry Number: 0

Grant and Affiliation Information for Enhanced protection against malaria by a chimeric merozoite surface protein vaccine.

AFFILIATION: Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.

Country: United States

AGENCY: United States NIAID

GRANT: R01AI35661

ACRONYM: AI

MEDLINETA: Infect Immun

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