IgG(4) Pf NPNA-1 a human anti-Plasmodium falciparum sporozoite monoclonal antibody cloned from a protected individual inhibits parasite invasion of hepatocytes.
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 IgG(4) 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 IgG(4) 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 IgG(4) is a promising candidate for evaluation for the prevention of malaria.
Chappel
Jonathan A
JA
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hollingdale
Michael R
MR
Kang
Angray S
AS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000913:Antibodies, Protozoan / Q000494:pharmacology*; D002460:Cell Line; D019084:Fluorescent Antibody Technique, Indirect; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D066298:In Vitro Techniques; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins