A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable of Eliciting High Titers of Neutralizing Antibodies in Immunized Rabbits

Authors

David H. Mulama, Beckman Research Institute of City of Hope
Lorraine Z. Mustvunguma, Beckman Research Institute of City of Hope
Jennifer Totonchy, Chapman UniversityFollow
Peng Ye, Beckman Research Institute of City of Hope
Joslyn Foley, Beckman Research Institute of City of Hope
Gabriela M. Escalante, Irell & Manella Graduate School of Biological Sciences of City of Hope
Esther Rodriguez, Beckman Research Institute of City of Hope
Ramina Nabiee, Chapman University
Murali Muniraju, Beckman Research Institute of City of Hope
Felix Wussow, Beckman Research Institute of City of Hope
Anne K. Barasa, Beckman Research Institute of City of Hope
Javier Gordon Ogembo, Beckman Research Institute of City of Hope

Document Type

Article

Publication Date

6-11-2019

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.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in Vaccine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Vaccine, volume 37, issue 30, in 2019. https://doi.org/10.1016/j.vaccine.2019.04.071

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Recommended Citation

Mulama DH, Mutsvunguma LZ, Totonchy J, et al. A multivalent Kaposi sarcoma-associated herpesvirus-like particle vaccine capable of eliciting high titers of neutralizing antibodies in immunized rabbits. Vaccine. 2019;37(30):4184-4194. https://doi.org/10.1016/j.vaccine.2019.04.071

Copyright

Elsevier

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.