Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis
Onchocerciasis (river blindness), caused by the filarial nematode <i>Onchocerca volvulus</i>, is a neglected tropical disease mainly of sub-Saharan Africa. Worldwide, an estimated 20.9 million individuals live with infection and a further 205 million are at risk of disease. Current contr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/6/861 |
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| author | Lisa Luu Germanus S. Bah Ndode Herman Okah-Nnane Catherine S. Hartley Alexandra F. Glover Tessa R. Walsh Lu-Yun Lian Bin Zhan Maria Elena Bottazzi David Abraham Nikolai Petrovsky Nicolas Bayang Bernard Tangwa Rene Billingwe Ayiseh Glory Enjong Mbah David D. Ekale Vincent N. Tanya Sara Lustigman Benjamin L. Makepeace John Graham-Brown |
| author_facet | Lisa Luu Germanus S. Bah Ndode Herman Okah-Nnane Catherine S. Hartley Alexandra F. Glover Tessa R. Walsh Lu-Yun Lian Bin Zhan Maria Elena Bottazzi David Abraham Nikolai Petrovsky Nicolas Bayang Bernard Tangwa Rene Billingwe Ayiseh Glory Enjong Mbah David D. Ekale Vincent N. Tanya Sara Lustigman Benjamin L. Makepeace John Graham-Brown |
| author_sort | Lisa Luu |
| collection | DOAJ |
| description | Onchocerciasis (river blindness), caused by the filarial nematode <i>Onchocerca volvulus</i>, is a neglected tropical disease mainly of sub-Saharan Africa. Worldwide, an estimated 20.9 million individuals live with infection and a further 205 million are at risk of disease. Current control methods rely on mass drug administration of ivermectin to kill microfilariae and inhibit female worm fecundity. The identification and development of efficacious vaccines as complementary preventive tools to support ongoing elimination efforts are therefore an important objective of onchocerciasis research. We evaluated the protective effects of co-administering leading <i>O. volvulus</i>-derived recombinant vaccine candidates (<i>Ov</i>-103 and <i>Ov</i>-RAL-2) with subsequent natural exposure to the closely related cattle parasite <i>Onchocerca ochengi</i>. Over a 24-month exposure period, vaccinated calves (<i>n</i> = 11) were shown to acquire infection and microfilaridermia at a significantly lower rate compared to unvaccinated control animals (<i>n</i> = 10). Furthermore, adult female worm burdens were negatively correlated with anti-<i>Ov</i>-103 and <i>Ov</i>-RAL-2 IgG1 and IgG2 responses. Peptide arrays identified several <i>Ov</i>-103 and <i>Ov</i>-RAL-2-specific epitopes homologous to those identified as human B-cell and helper T-cell epitope candidates and by naturally-infected human subjects in previous studies. Overall, this study demonstrates co-administration of <i>Ov</i>-103 and <i>Ov</i>-RAL-2 with Montanide™ ISA 206 VG is highly immunogenic in cattle, conferring partial protection against natural challenge with <i>O. ochengi</i>. The strong, antigen-specific IgG1 and IgG2 responses associated with vaccine-induced protection are highly suggestive of a mixed Th1/Th2 associated antibody responses. Collectively, this evidence suggests vaccine formulations for human onchocerciasis should aim to elicit similarly balanced Th1/Th2 immune responses. |
| first_indexed | 2024-03-09T22:17:11Z |
| format | Article |
| id | doaj.art-50a1373c156e48e18dca51fca88b9831 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:17:11Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-50a1373c156e48e18dca51fca88b98312023-11-23T19:20:27ZengMDPI AGVaccines2076-393X2022-05-0110686110.3390/vaccines10060861Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human OnchocerciasisLisa Luu0Germanus S. Bah1Ndode Herman Okah-Nnane2Catherine S. Hartley3Alexandra F. Glover4Tessa R. Walsh5Lu-Yun Lian6Bin Zhan7Maria Elena Bottazzi8David Abraham9Nikolai Petrovsky10Nicolas Bayang11Bernard Tangwa12Rene Billingwe Ayiseh13Glory Enjong Mbah14David D. Ekale15Vincent N. Tanya16Sara Lustigman17Benjamin L. Makepeace18John Graham-Brown19Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonInstitute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKInstitute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKInstitute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKInstitute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5RF, UKNational School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USANational School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USADepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USAFlinders Medical Centre, Adelaide 5042, AustraliaL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonBiotechnology Unit, University of Buea, Buea P.O. Box 63, CameroonDepartment of Biology, Higher Teacher Training College (HTTC), The University of Bamenda, Bambili P.O. Box 39, CameroonL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonL’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, CameroonMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USAInstitute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKInstitute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UKOnchocerciasis (river blindness), caused by the filarial nematode <i>Onchocerca volvulus</i>, is a neglected tropical disease mainly of sub-Saharan Africa. Worldwide, an estimated 20.9 million individuals live with infection and a further 205 million are at risk of disease. Current control methods rely on mass drug administration of ivermectin to kill microfilariae and inhibit female worm fecundity. The identification and development of efficacious vaccines as complementary preventive tools to support ongoing elimination efforts are therefore an important objective of onchocerciasis research. We evaluated the protective effects of co-administering leading <i>O. volvulus</i>-derived recombinant vaccine candidates (<i>Ov</i>-103 and <i>Ov</i>-RAL-2) with subsequent natural exposure to the closely related cattle parasite <i>Onchocerca ochengi</i>. Over a 24-month exposure period, vaccinated calves (<i>n</i> = 11) were shown to acquire infection and microfilaridermia at a significantly lower rate compared to unvaccinated control animals (<i>n</i> = 10). Furthermore, adult female worm burdens were negatively correlated with anti-<i>Ov</i>-103 and <i>Ov</i>-RAL-2 IgG1 and IgG2 responses. Peptide arrays identified several <i>Ov</i>-103 and <i>Ov</i>-RAL-2-specific epitopes homologous to those identified as human B-cell and helper T-cell epitope candidates and by naturally-infected human subjects in previous studies. Overall, this study demonstrates co-administration of <i>Ov</i>-103 and <i>Ov</i>-RAL-2 with Montanide™ ISA 206 VG is highly immunogenic in cattle, conferring partial protection against natural challenge with <i>O. ochengi</i>. The strong, antigen-specific IgG1 and IgG2 responses associated with vaccine-induced protection are highly suggestive of a mixed Th1/Th2 associated antibody responses. Collectively, this evidence suggests vaccine formulations for human onchocerciasis should aim to elicit similarly balanced Th1/Th2 immune responses.https://www.mdpi.com/2076-393X/10/6/861river blindnessonchocerciasisNTDsvaccineimmunityOne Health |
| spellingShingle | Lisa Luu Germanus S. Bah Ndode Herman Okah-Nnane Catherine S. Hartley Alexandra F. Glover Tessa R. Walsh Lu-Yun Lian Bin Zhan Maria Elena Bottazzi David Abraham Nikolai Petrovsky Nicolas Bayang Bernard Tangwa Rene Billingwe Ayiseh Glory Enjong Mbah David D. Ekale Vincent N. Tanya Sara Lustigman Benjamin L. Makepeace John Graham-Brown Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis Vaccines river blindness onchocerciasis NTDs vaccine immunity One Health |
| title | Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis |
| title_full | Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis |
| title_fullStr | Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis |
| title_full_unstemmed | Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis |
| title_short | Co-Administration of Adjuvanted Recombinant <i>Ov</i>-103 and <i>Ov</i>-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine <i>Onchocerca ochengi</i> Infection Model of Human Onchocerciasis |
| title_sort | co administration of adjuvanted recombinant i ov i 103 and i ov i ral 2 vaccines confer protection against natural challenge in a bovine i onchocerca ochengi i infection model of human onchocerciasis |
| topic | river blindness onchocerciasis NTDs vaccine immunity One Health |
| url | https://www.mdpi.com/2076-393X/10/6/861 |
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