Abstract
The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit vaccines.
Highlights
Despite considerable progress in efforts to control the transmission of malaria, the disease continues to cause approximately 225 million cases of clinical illness and nearly eight hundred thousand deaths each year [1]
Immunization of mice with our previously reported AdHu5 prime – modified vaccinia virus Ankara (MVA) boost regime [21,23,25] resulted in high, antigen-specific antibody titers that reacted with Pfs25 protein expressed by the Pfs25DR3 ookinete
chimpanzee adenovirus 63 (ChAd63) Pfs25 prime appeared to be as effective as AdHu5 Pfs25 as assessed by ELISA
Summary
Despite considerable progress in efforts to control the transmission of malaria, the disease continues to cause approximately 225 million cases of clinical illness and nearly eight hundred thousand deaths each year [1]. This, along with the introduction of partially effective pre-erythrocytic control measures (e.g. ITNs, indoor residual spraying (IRS), artemisinin-based combination therapies (ACTs)), has led to a renewed interest in developing transmission-blocking vaccines (TBVs) – an approach that intercepts the P. falciparum life-cycle within the mosquito. This ‘‘community vaccination’’ approach would complement partially effective pre-erythrocytic control measures, and the development of an effective TBV is widely viewed as essential for breaking the transmission cycle of malaria, especially following recent ambitious calls that the malaria community should aim for elimination or eradication [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
