IgG4 Pf NPNA-1 a human anti-Plasmodium falciparum sporozoite monoclonal antibody cloned from a protected individual inhibits parasite invasion of hepatocytes
Affiliations: [a] Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA | [b] Department of Biology, University of Leeds, UK, MRH | [c] Current address: MRH, Global Affairs, NIAID, 9000 Rockville Pike, Bethesda, MD 20852, USA. E-mail: [email protected] | [d] Current address: ASK, Antibody Technology, Avanir Pharmaceuticals, 11388 Sorrento Valley Road, San Diego, CA 92121, USA. Tel.: +1 858 622 5294; Fax: +1 858 658 7458; E-mail: [email protected]
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Corresponding author.
Abstract: Malaria is one of the world's most devastating diseases, and Plasmodium falciparum (Pf) causes significant mortalities particularly in Sub-Saharan Africa. The rise and spread of multi-drug resistant strains of the parasite has coincided with an era of increased travel to malaria endemic regions. In the absence of an effective vaccine against malaria it may be possible to utilize human monoclonal antibodies against the stage transmitted by mosquito bites (sporozoites) as a prophylactic to prevent infection. We report the characterization of an engineered human IgG4 monoclonal antibody against Pf sporozoite cloned from a protected individual recognized the sporozoite surface and inhibited sporozoite invasion of human hepatocytes in vitro. The fully human monoclonal antibody PfNPNA-1 IgG4 against (NPNA)3 specifically labels Plasmodium falciparum in an IFA. This antibody also inhibits Plasmodium falciparum sporozoite invasion of human hepatocytes HepG2-A16 in a dose dependent manner in an in vitro assay. PfNPNA-1 IgG4 is a promising candidate for evaluation for the prevention of malaria.
Keywords: Plasmodium falciparum, sporozoite, human monoclonal antibodies
