Adjuvanted Fusion Protein Vaccine Induces Durable Immunity to Onchocerca volvulus in Mice and Non-Human Primates

Author:

Ryan Nathan M.1ORCID,Hess Jessica A.1,Robertson Erica J.1,Tricoche Nancy2,Turner Cheri3,Davis Jenn3,Petrovsky Nikolai4ORCID,Ferguson Melissa5,Rinaldi William J.5,Wong Valerie M.6,Shimada Ayako7ORCID,Zhan Bin8ORCID,Bottazzi Maria Elena8ORCID,Makepeace Benjamin L.9ORCID,Gray Sean A.3,Carter Darrick3ORCID,Lustigman Sara2,Abraham David1ORCID

Affiliation:

1. Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA

2. Laboratory of Molecular Parasitology, Lindsey F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA

3. PAI Life Sciences Inc., Seattle, WA 98102, USA

4. Vaxine Pty Ltd., Bedford Park, Adelaide, SA 5042, Australia

5. Alpha Genesis Inc., Yemassee, SC 29945, USA

6. IDEXX BioAnalytics, West Sacramento, CA 95605, USA

7. Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA

8. Texas Children’s Hospital Center for Vaccine Development, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA

9. Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Liverpool L3 5RF, UK

Abstract

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with Ov-FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that Ov-FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors.

Funder

National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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