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

<div><p>Background</p><p>The <i>Brugia malayi Bm</i>-103 and <i>Bm</i>-RAL-2 proteins are orthologous to <i>Onchocerca volvulus Ov</i>-103 and <i>Ov</i>-RAL-2, and which were selected as the best candidates for the development of an <i>O</i>. <i>volvulus</i> vaccine. The <i>B</i>. <i>malayi</i> gerbil model was used to confirm the efficacy of these <i>Ov</i> vaccine candidates on adult worms and to determine whether their combination is more efficacious.</p><p>Methodology and Principle Findings</p><p>Vaccine efficacy of recombinant <i>Bm</i>-103 and <i>Bm</i>-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with <i>Bm</i>-103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi), respectively, and vaccination with <i>Bm</i>-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 <i>Bm</i>-103 and <i>Bm</i>-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 <i>Bm</i>-103 and <i>Bm</i>-RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with <i>Bm</i>-103 and <i>Bm</i>-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 <i>Bm</i>-103 and <i>Bm</i>-RAL-2 individually, concurrently or as a fusion protein killed third stage larvae <i>in vitro</i> when combined with peritoneal exudate cells.</p><p>Conclusion</p><p>Although vaccination with <i>Bm</i>-103 and <i>Bm</i>-RAL-2 individually conferred protection against <i>B</i>. <i>malayi</i> infection in gerbils, a more consistent and enhanced protection was induced by vaccination with <i>Bm</i>-103 and <i>Bm-</i>RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted.</p>