Comparable antigenicity and immunogenicity of oligomeric forms of a novel, acute HIV-1 subtype C gp145 envelope for use in preclinical and clinical vaccine research

Lindsay Wieczorek, Shelly J. Krebs, Vaniambadi Kalyanaraman, Stephen Whitney, Sodsai Tovanabutra, Carlos G. Moscoso, Eric Sanders-Buell, Constance Williams, Bonnie Slike, Sebastian Molnar, Vincent Dussupt, S. Munir Alam, Agnes Laurence Chenine, Tina Tong, Edgar L. Hill, Hua Xin Liao, Michael Hoelscher, Leonard Maboko, Susan Zolla-Pazner, Barton F. HaynesMichael Pensiero, Francine McCutchan, Shawyon Malek-Salehi, R. Holland Cheng, Merlin L. Robb, Thomas VanCott, Nelson L. Michael, Mary A. Marovich, Carl R. Alving, Gary R. Matyas, Mangala Rao, Victoria R. Polonis

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of crosssubtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine.

Original languageEnglish (US)
Pages (from-to)7478-7493
Number of pages16
JournalJournal of Virology
Volume89
Issue number15
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Wieczorek, L., Krebs, S. J., Kalyanaraman, V., Whitney, S., Tovanabutra, S., Moscoso, C. G., Sanders-Buell, E., Williams, C., Slike, B., Molnar, S., Dussupt, V., Munir Alam, S., Chenine, A. L., Tong, T., Hill, E. L., Liao, H. X., Hoelscher, M., Maboko, L., Zolla-Pazner, S., ... Polonis, V. R. (2015). Comparable antigenicity and immunogenicity of oligomeric forms of a novel, acute HIV-1 subtype C gp145 envelope for use in preclinical and clinical vaccine research. Journal of Virology, 89(15), 7478-7493. https://doi.org/10.1128/JVI.00412-15