Immunization of Mice with Virus-Like Vesicles of Kaposi Sarcoma-Associated Herpesvirus Reveals a Role for Antibodies Targeting ORF4 in Activating Complement-Mediated Neutralization

Alex K. Lam, Romin Roshan, Wendell Miley, Nazzarena Labo, James Zhen, Andrew P. Kurland, Celine Cheng, Haigen Huang, Pu Lin Teng, Claire Harelson, Danyang Gong, Ying K. Tam, Caius G. Radu, Marta Epeldegui, Jeffrey R. Johnson, Z. Hong Zhou, Denise Whitby, Ting Ting Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions. Here, we investigated the immunogenicity of KSHV VLVs produced from a viral mutant that was defective in capsid formation and DNA packaging. Mice immunized with adjuvanted VLVs generated KSHV-specific T cell and antibody responses. Neutralization of KSHV infection by the VLV immune serum was low but was markedly enhanced in the presence of the complement system. Complement-enhanced neutralization and complement deposition on KSHV-infected cells was dependent on antibodies targeting viral open reading frame 4 (ORF4). However, limited complement-mediated enhancement was detected in the sera of a small cohort of KSHV-infected humans which contained few neutralizing antibodies. Therefore, vaccination that induces antibody effector functions can potentially improve infection-induced humoral immunity. Overall, our study highlights a potential benefit of engaging complement-mediated antibody functions in future KSHV vaccine development.

Original languageEnglish
JournalJournal of Virology
Volume97
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • KSHV
  • antibody function
  • complement
  • neutralizing antibodies
  • vaccine

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