Use of a recombinant gamma-2 herpesvirus vaccine vector against dengue virus in rhesus monkeys

Georg F. Bischof, Diogo M. Magnani, Michael Ricciardi, Young C. Shin, Aline Domingues, Varian K. Bailey, Lucas Gonzalez-Nieto, Eva G. Rakasz, David I. Watkins, Ronald C. Desrosiers

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Research on vaccine approaches that can provide long-term protection against dengue virus infection is needed. Here we describe the construction, immunogenicity, and preliminary information on the protective capacity of recombinant, replication-competent rhesus monkey rhadinovirus (RRV), a persisting herpesvirus. One RRV construct expressed nonstructural protein 5 (NS5), while a second recombinant expressed a soluble variant of the E protein (E85) of dengue virus 2 (DENV2). Four rhesus macaques received a single vaccination with a mixture of both recombinant RRVs and were subsequently challenged 19 weeks later with 1 × 105 PFU of DENV2. During the vaccine phase, plasma of all vaccinated monkeys showed neutralizing activity against DENV2. Cellular immune responses against NS5 were also elicited, as evidenced by major histocompatibility complex class I (MHC-I) tetramer staining in the one vaccinated monkey that was Mamu-A*01 positive. Unlike two of two unvaccinated controls, two of the four vaccinated monkeys showed no detectable viral RNA sequences in plasma after challenge. One of these two monkeys also showed no anamnestic increases in antibody levels following challenge and thus appeared to be protected against the acquisition of DENV2 following highdose challenge. Continued study will be needed to evaluate the performance of herpesviral and other persisting vectors for achieving long-term protection against dengue virus infection.

Original languageEnglish (US)
Article numbere00525-17
JournalJournal of virology
Volume91
Issue number16
DOIs
StatePublished - Aug 1 2017

Keywords

  • DENV vaccine
  • Herpesviral vector
  • Live-vector vaccines
  • Recombinant vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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