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
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
Affiliations
Lisa Luu
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
Germanus S. Bah
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Ndode Herman Okah-Nnane
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Catherine S. Hartley
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
Alexandra F. Glover
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
Tessa R. Walsh
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
Lu-Yun Lian
Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5RF, UK
Bin Zhan
National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Maria Elena Bottazzi
National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA
David Abraham
Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
Nikolai Petrovsky
Flinders Medical Centre, Adelaide 5042, Australia
Nicolas Bayang
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Bernard Tangwa
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Rene Billingwe Ayiseh
Biotechnology Unit, University of Buea, Buea P.O. Box 63, Cameroon
Glory Enjong Mbah
Department of Biology, Higher Teacher Training College (HTTC), The University of Bamenda, Bambili P.O. Box 39, Cameroon
David D. Ekale
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Vincent N. Tanya
L’Institut de Recherche Agricole Pour le Deéveloppement (IRAD), Yaoundé 2123, Cameroon
Sara Lustigman
Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA
Benjamin L. Makepeace
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
John Graham-Brown
Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK
Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, 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 O. volvulus-derived recombinant vaccine candidates (Ov-103 and Ov-RAL-2) with subsequent natural exposure to the closely related cattle parasite Onchocerca ochengi. Over a 24-month exposure period, vaccinated calves (n = 11) were shown to acquire infection and microfilaridermia at a significantly lower rate compared to unvaccinated control animals (n = 10). Furthermore, adult female worm burdens were negatively correlated with anti-Ov-103 and Ov-RAL-2 IgG1 and IgG2 responses. Peptide arrays identified several Ov-103 and Ov-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 Ov-103 and Ov-RAL-2 with Montanide™ ISA 206 VG is highly immunogenic in cattle, conferring partial protection against natural challenge with O. ochengi. 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.
