Assessment of Babesia bovis 6cys A and 6cys B as components of transmission blocking vaccines for babesiosis.

BACKGROUND: Babesia bovis reproduces sexually in the gut of its tick vector Rhipicephalus microplus, which involves expression of 6cys A and 6cys B proteins. Members of the widely conserved 6cys superfamily are candidates for transmission blocking vaccines (TBV), but intricacies in the immunogenicity of the 6cys proteins in the related Plasmodium parasites required the identification of transmission blocking domains in these molecules for vaccine design. Hereby, the immunogenic efficacy of recombinant (r) B. bovis 6cys A and B proteins as a TBV formulation was studied. METHODS: The immunogenicity of r6cys A and 6cys B proteins expressed in a eukaryotic system was evaluated in a cattle immunization trial (3 immunized and 3 control calves). A B. bovis sexual stage induction in vitro inhibition assay to assess the ability of antibodies to block the production of sexual forms by the parasite was developed. RESULTS: Immunized cattle generated antibodies against r6cys A and r6cys B that were unable to block sexual reproduction of the parasite in ticks. Additionally, these antibodies also failed in recognizing native 6cys A and 6cys B and peptides representing 6cys A and 6cys B functional domains and in inhibiting the development of sexual forms in an in vitro induction system. In contrast, rabbit antibodies generated against synthetic peptides representing predicted B-cell epitopes of 6cys A and 6cys B recognized recombinant and native forms of both 6cys proteins as well as peptides representing 6cys A and 6cys B functional domains and were able to neutralize development of sexual forms of the parasite in vitro. CONCLUSIONS: These data, combined with similar work performed on Plasmodium 6cys proteins, indicate that an effective 6cys protein-based TBV against B. bovis will require identifying and targeting selected regions of proteins containing epitopes able to reduce transmission.

Economic and practical challenges to the formulation of vaccines against endemic infectious diseases such as malaria.

Herein, we analyze in general the current vaccine market and identify potential factors driving and modulating supply and demand for vaccines. An emphasis is placed on changes in regulation in the last 20 years which have led to increased indirect costs of production, and which can create a barrier against the timely use of technological advances to reduce direct costs. Other defining industry characteristics, such as firm numbers and sizes, cost and pricing strategies, nature extent and impact of Government involvement and international regulation are noted. These considerations, far from being removed from basic vaccine research, influence its ability to achieve aims that can be then progressed into effective vaccine products. We discuss specifically the development of particulate vaccines against malaria, a major lethal disease and health problem prevalent in Africa, including some key economic and methodological challenges and opportunities. We note some practical issues blocking the development of effective particulate vaccines for the Third World, mainly driven by the regulatory spiral noted above.