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.

Authors

Sridhar Arumugam, Department of Pathobiological Sciences, LSU School of Veterinary Medicine, Louisiana State UniversityFollow
Junfei Wei, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine
Zhuyun Liu, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine
David Abraham, Department of Microbiology and Immunology, Sidney Kimmel Medical College at Thomas Jefferson UniversityFollow
Aaron Bell, Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center
Maria Elena Bottazzi, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical MedicineFollow
Peter J Hotez, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical MedicineFollow
Bin Zhan, Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical MedicineFollow
Sara Lustigman, Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood CenterFollow
Thomas R Klei, Department of Pathobiological Sciences, LSU School of Veterinary Medicine, Louisiana State UniversityFollow

Document Type

Article

Publication Date

4-5-2016

Comments

This article has been peer reviewed. It was published in: PLoS Neglected Tropical Diseases.

Volume 10, Issue 4, 5 April 2016, Article number e0004586.

The published version is available at DOI: 10.1371/journal.pntd.0004586

Copyright © 2016 Arumugam et al

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Recommended Citation

Arumugam, Sridhar; Wei, Junfei; Liu, Zhuyun; Abraham, David; Bell, Aaron; Bottazzi, Maria Elena; Hotez, Peter J; Zhan, Bin; Lustigman, Sara; and Klei, Thomas R, "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." (2016). Department of Microbiology and Immunology Faculty Papers. Paper 77.
https://jdc.jefferson.edu/mifp/77

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

27045170