Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

M. Giel-Moloney, M. Esteban, B. H. Oakes, M. Vaine, B. Asbach, R. Wagner, G. J. Mize, A. G. Spies, J. McElrath, M. Perreau, T. Roger, A. Ives, T. Calandra, D. Weiss, B. Perdiguero, K. V. Kibler, B. Jacobs, S. Ding, G. D. Tomaras, D. C. MontefioriG. Ferrari, N. L. Yates, M. Roederer, S. F. Kao, K. E. Foulds, B. T. Mayer, C. Bennett, R. Gottardo, M. Parrington, J. Tartaglia, S. Phogat, G. Pantaleo, H. Kleanthous, K. V. Pugachev

Research output: Contribution to journalArticle

Abstract

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

Original languageEnglish (US)
Article number20005
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector'. Together they form a unique fingerprint.

  • Cite this

    Giel-Moloney, M., Esteban, M., Oakes, B. H., Vaine, M., Asbach, B., Wagner, R., Mize, G. J., Spies, A. G., McElrath, J., Perreau, M., Roger, T., Ives, A., Calandra, T., Weiss, D., Perdiguero, B., Kibler, K. V., Jacobs, B., Ding, S., Tomaras, G. D., ... Pugachev, K. V. (2019). Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector. Scientific reports, 9(1), [20005]. https://doi.org/10.1038/s41598-019-56550-4