XXXX by sporozoite challenge induces high functional antibody titres against blood stage antigens after a DNA prime, poxvirus boost vaccination strategy in @entity2608 .

@entity2608 @entity281 @entity31365 @entity311
BACKGROUND: A DNA prime, poxvirus (COPAK) boost vaccination regime with four antigens, i.e. a combination of two @entity31365 sporozoite (csp/ssp2) and two blood stage (ama1/msp142) genes, leads to self-limited parasitaemia in 60% of @entity2608 and survival from an otherwise lethal @entity281 with @entity31365 . In the present study, the role of the blood stage antigens in protection was studied in depth, focusing on antibody formation against the blood stage antigens and the functionality thereof. METHODS: @entity2608 were immunized with the four-component vaccine and subsequently challenged i.v. with 100 @entity31365 sporozoites. During immunization and challenge, antibody titres against the two blood stage antigens were determined, as well as the in vitro growth inhibition capacity of those antibodies. Antigen reversal experiments were performed to determine the relative contribution of antibodies against each of the two blood stage antigens to the inhibition. RESULTS: After vaccination, PkAMA1 and PkMSP1       antibody titres in vaccinated animals were low, which was reflected in low levels of inhibition by these antibodies as determined by in vitro inhibition assays. Interestingly, after sporozoite challenge antibody titres against blood stage antigens were boosted over 30-fold in both protected and not protected animals. The in vitro inhibition levels increased to high levels (median inhibitions of 59% and 56% at 6 mg/mL total IgG, respectively). As growth inhibition levels were not significantly different between protected and not protected animals, the ability to control @entity281 appeared cannot be explained by GIA levels. Judged by in vitro antigen reversal growth inhibition assays, over 85% of the inhibitory activity of these antibodies was directed against PkAMA1. CONCLUSIONS: This is the first report that demonstrates that a DNA prime/poxvirus boost vaccination regimen induces low levels of @entity311 parasite growth inhibitory antibodies, which are boosted to high levels upon challenge. No association could, however, be established between the levels of inhibitory capacity in vitro and protection, either after vaccination or after challenge.
