A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits |
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| Institution: | 1. Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, United States;2. Biological Sciences Department, Masinde Muliro University of Science and Technology, Kakamega, Kenya;3. Chapman University, School of Pharmacy, Irvine, CA, United States;4. Irell & Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, United States;5. Department of Human Pathology, University of Nairobi, Nairobi, Kenya;1. Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, United States;2. FDA, Center for Drug Evaluation and Research, Silver Spring, MD, United States;3. Division of Allergy-Immunology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States;4. HealthCore, Alexandria, VA, United States;5. Comprehensive Health Insight, Humana, Louisville, KY, United States;6. Aetna, Blue Bell, PA, United States;7. Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States;1. Johns Hopkins Berman Institute of Bioethics, Johns Hopkins University, USA;2. Department of International Health, Johns Hopkins University Bloomberg School of Public Health, USA;3. Johns Hopkins Center for Immunization Research, Johns Hopkins School of Public Health, USA;4. Institute for Vaccine Safety, Johns Hopkins University Bloomberg School of Public Health, USA;5. Department of Health, Behavior & Society, Johns Hopkins University Bloomberg School of Public Health, USA;6. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, USA;1. School of Biological and Agricultural Engineering, Jilin University, 5988 Renmin Street, Changchun 130022, PR China;2. Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, 5988 Renmin Street, Changchun 130022, PR China;3. School of Management, Jilin University, 5988 Renmin Street, Changchun 130022, PR China;1. INSERM U976 HIPI, équipe INSIGHT, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France;2. Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France;3. National Reference Center for Castleman disease, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France;4. Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INESRM UMR 1163, Imagine Institute, Université Paris Cité Paris, France;5. Department of Internal Medicine, Hôpital Bichat, AP-HP, Université Paris Cité, Paris, France;6. Laboratory of Immunology, Hôpital Robert Debré, AP-HP, Université Paris Cité, Paris, France;7. Department of Pathology, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France;8. Laboratory of Virology, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France;9. Department of Internal Medicine, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Cité, Paris, France;10. Department of Dermatology, Hôpital Saint-Louis, AP-HP, Université Paris Cité, Paris, France;11. Department of Clinical Hematology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France;1. Cincinnati Children''s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States;2. Baylor College of Medicine, Houston, TX, United States;3. Vanderbilt University Medical Center, Nashville, TN, United States;4. University of Texas Medical Branch at Galveston, Galveston, TX, United States;5. University of Texas Health Science Center at Houston, Houston, TX, United States;6. University of South Carolina School of Medicine, Columbia, SC, United States;7. Columbia University, New York Presbyterian Hospital, New York City, NY, United States;8. Sanofi Pasteur, Marcy L’Etoile, France;9. The Emmes Corporation, Rockville, MD, United States |
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| Abstract: | Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B cell lines (60–90% at the highest concentration tested). These findings suggest that KSHV-LPs may be an ideal platform for developing a safe and effective prophylactic KSHV vaccine. We envision performing future studies in animal models that are susceptible to KSHV infection, to determine correlates of immune protection in vivo. |
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| Keywords: | Kaposi sarcoma-associated human herpesvirus Kaposi sarcoma Prophylactic vaccine Glycoproteins Neutralizing antibody titers Rabbits |
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