title: Evaluation of an in vitro assay aimed at measuring protective antibodies against sporozoites.
abstract: We have evaluated the in vitro biological activities of antibodies directed against sporozoites and compared them with their capacity to protect against challenge with both human and rodent malaria. The anti-Plasmodium falciparum antibodies evaluated with the test included monoclonal antibodies (MAbs) NFS1 and NFS2 as well as polyclonal antibodies contained in human hyperimmune sera directed against sporozoites of P. falciparum. The inhibitory effect of these antibodies was dependent on their concentration. However, total inhibition was not observed except occasionally with highly concentrated MAbs (10-100 micrograms/ml). Strong but also incomplete inhibition was observed with sera from humans living in hyperendemic areas. In the P. yoelii rodent system, we tested sera from mice immunized with subunit vaccines. None of these mice were protected in vivo against challenge with 40-200 sporozoites. In vitro only a sub-total inhibition was achieved (maximum 91% at 1:10 serum dilution). In contrast, we tested sera from mice that received NYS1, an IgG3 MAb, in passive transfer and were protected against challenge with 5000 sporozoites. At 1:10 dilution, 100% inhibition was achieved in vitro while IFA titres from these mice were similar to those of vaccinated mice. These data show a close correlation between in vivo and in vitro findings and thus suggest that the inhibition of liver-stage development assay (ILSDA) appears appropriate to evaluate the potential of antibodies.
authors.affiliation: Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5055.
authors.forename: S
authors.initials: S
authors.lastname: Mellouk
authors.forename: N
authors.initials: N
authors.lastname: Berbiguier
authors.forename: P
authors.initials: P
authors.lastname: Druilhe
authors.forename: M
authors.initials: M
authors.lastname: Sedegah
authors.forename: B
authors.initials: B
authors.lastname: Galey
authors.forename: L
authors.initials: L
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Leef
authors.forename: Y
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: C
authors.initials: C
authors.lastname: Paul
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000302:isolation & purification*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology; D008288:Malaria / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007106:Immune Sera