Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 212, Issue 7, Pages 1111-1119Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv154
Keywords
antibodies; CSP; malaria; P. falciparum; sporozoites; vaccine
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Funding
- NIAID/Division of Microbiology and Infectious Diseases [AI-N01-045210]
- Nationals Institutes of Health/NIAID [AI44375, AI056840]
- Johns Hopkins Malaria Research Institute
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Studies in animals and human volunteers demonstrate that antibodies against the repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate sporozoite infection. However, the realization that the N- and C-terminal regions flanking the repeats play essential roles in parasite infectivity raised the possibility that they could be targeted by protective antibodies. We characterized a monoclonal antibody (mAb5D5) specific for the N- terminus of the P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5 strongly inhibits the in vivo infection of sporozoites expressing the N- terminus of P. falciparum CSP, and this protection is greatly enhanced when combined with antirepeat antibodies. Our results show that antibodies interfering with molecular processes required for parasite infectivity can exert a strong in vivo protective activity and indicate that pre-erythrocytic vaccines against Plasmodium should include the CSP N- terminal region.
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