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.

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 candidat...

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Published in:PLOS Neglected Tropical Diseases
Main Authors: Sridhar Arumugam, Junfei Wei, Zhuyun Liu, David Abraham, Aaron Bell, Maria Elena Bottazzi, Peter J Hotez, Bin Zhan, Sara Lustigman, Thomas R Klei
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2016
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0004586
https://doaj.org/article/95bd6f868063411c96b116b02278eee9
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spelling ftdoajarticles:oai:doaj.org/article:95bd6f868063411c96b116b02278eee9 2023-05-15T15:17:21+02:00 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. Sridhar Arumugam Junfei Wei Zhuyun Liu David Abraham Aaron Bell Maria Elena Bottazzi Peter J Hotez Bin Zhan Sara Lustigman Thomas R Klei 2016-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004586 https://doaj.org/article/95bd6f868063411c96b116b02278eee9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4821550?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004586 https://doaj.org/article/95bd6f868063411c96b116b02278eee9 PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004586 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004586 2022-12-31T03:53:58Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 4 e0004586
institution Open Polar
collection Directory of Open Access Journals: DOAJ Articles
op_collection_id ftdoajarticles
language English
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Sridhar Arumugam
Junfei Wei
Zhuyun Liu
David Abraham
Aaron Bell
Maria Elena Bottazzi
Peter J Hotez
Bin Zhan
Sara Lustigman
Thomas R Klei
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.
topic_facet Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
description 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.
format Article in Journal/Newspaper
author Sridhar Arumugam
Junfei Wei
Zhuyun Liu
David Abraham
Aaron Bell
Maria Elena Bottazzi
Peter J Hotez
Bin Zhan
Sara Lustigman
Thomas R Klei
author_facet Sridhar Arumugam
Junfei Wei
Zhuyun Liu
David Abraham
Aaron Bell
Maria Elena Bottazzi
Peter J Hotez
Bin Zhan
Sara Lustigman
Thomas R Klei
author_sort Sridhar Arumugam
title 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.
title_short 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_sort 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.
publisher Public Library of Science (PLoS)
publishDate 2016
url https://doi.org/10.1371/journal.pntd.0004586
https://doaj.org/article/95bd6f868063411c96b116b02278eee9
geographic Arctic
geographic_facet Arctic
genre Arctic
genre_facet Arctic
op_source PLoS Neglected Tropical Diseases, Vol 10, Iss 4, p e0004586 (2016)
op_relation http://europepmc.org/articles/PMC4821550?pdf=render
https://doaj.org/toc/1935-2727
https://doaj.org/toc/1935-2735
1935-2727
1935-2735
doi:10.1371/journal.pntd.0004586
https://doaj.org/article/95bd6f868063411c96b116b02278eee9
op_doi https://doi.org/10.1371/journal.pntd.0004586
container_title PLOS Neglected Tropical Diseases
container_volume 10
container_issue 4
container_start_page e0004586
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