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Background  The  Brugia malayi Bm -103 and  Bm -RAL-2 proteins are orthologous to  Onchocerca volvulus Ov -103 and  Ov -RAL-2, and which were selected as the best candidates for the development of an  O .  volvulus  vaccine. The  B .  malayi  gerbil model was used to confirm the efficacy of these  Ov  vaccine candidates on adult worms and to determine whether their combination is more efficacious.    Methodology and Principle Findings  Vaccine efficacy of recombinant  Bm -103 and  Bm -RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with  Bm -103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi), respectively, and vaccination with  Bm -RAL-2 resulted in worm reductions of 42%, 22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion protein comprised of  Bm -103 and  Bm -RAL-2 resulted in improved efficacy with significant reduction of worm burden of 51% and 49% at 90 dpi, as did the concurrent vaccination with  Bm -103 and  Bm -RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with  Bm -103 and  Bm -RAL-2 as a fusion protein or concurrently not only induced a significant worm reduction of 61% and 42%, respectively, at 150 dpi, but also significantly reduced the fecundity of female worms as determined by embryograms. Elevated levels of antigen-specific IgG were observed in all vaccinated gerbils. Serum from gerbils vaccinated with  Bm -103 and  Bm -RAL-2 individually, concurrently or as a fusion protein killed third stage larvae  in vitro  when combined with peritoneal exudate cells.    Conclusion  Although vaccination with  Bm -103 and  Bm -RAL-2 individually conferred protection against  B .  malayi  infection in gerbils, a more consistent and enhanced protection was induced by vaccination with  Bm -103 and  Bm- RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted.

plos neglected tropical diseases

Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection