Ancestral and consensus envelope immunogens for HIV-1 subtype C

Denise L. Kothe, Yingying Li, Julie M. Decker, Frederic Bibollet-Ruche, Kenneth P. Zammit, Maria G. Salazar, Yalu Chen, Zhiping Weng, Eric A Weaver, Feng Gao, Barton F. Haynes, George M. Shaw, Bette T.M. Korber, Beatrice H. Hahn

Research output: Contribution to journalArticle

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Abstract

Immunogens based on "centralized" (ancestral or consensus) HIV-1 sequences minimize the genetic distance between vaccine strains and contemporary viruses and should thus elicit immune responses that recognize a broader spectrum of viral variants. However, the biologic, antigenic and immunogenic properties of such inferred gene products have to be validated experimentally. Here, we report the construction and characterization of the first full-length ancestral (AncC) and consensus (ConC) env genes of HIV-1 (group M) subtype C. The codon-usage-optimized genes expressed high levels of envelope glycoproteins that were incorporated into HIV-1 virions, mediated infection via the CCR5 co-receptor and retained neutralizing epitopes as recognized by plasma from patients with chronic HIV-1 subtype C infection. Guinea pigs immunized with AncC and ConC env DNA developed high titer binding, but no appreciable homologous or heterologous neutralizing antibodies. When tested by immunoblot analysis, sera from AncC and ConC env immunized guinea pigs recognized a greater number of primary subtype C envelope glycoproteins than sera from guinea pigs immunized with a contemporary subtype C env control. Mice immunized with AncC and ConC env DNA developed gamma interferon T cell responses that recognized overlapping peptides from the cognate ConC and a heterologous subtype C Env control. Thus, both AncC and ConC env genes expressed functional envelope glycoproteins that were immunogenic in laboratory animals and elicited humoral and cellular immune responses of comparable breadth and magnitude. These results establish the utility of centralized HIV-1 subtype C Env immunogens and warrant their continued evaluation as potential components of future AIDS vaccines.

Original languageEnglish (US)
Pages (from-to)438-449
Number of pages12
JournalVirology
Volume352
Issue number2
DOIs
StatePublished - Sep 1 2006

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HIV-1
env Genes
Guinea Pigs
Glycoproteins
CCR5 Receptors
Heterophile Antibodies
AIDS Vaccines
DNA
Laboratory Animals
Humoral Immunity
Infection
Neutralizing Antibodies
Serum
Cellular Immunity
Codon
Virion
Genes
Interferon-gamma
Epitopes
Vaccines

Keywords

  • Centralized HIV-1 immunogens
  • HIV-1 envelope glycoprotein
  • HIV-1 genetic variation
  • Subtype C

ASJC Scopus subject areas

  • Virology

Cite this

Kothe, D. L., Li, Y., Decker, J. M., Bibollet-Ruche, F., Zammit, K. P., Salazar, M. G., ... Hahn, B. H. (2006). Ancestral and consensus envelope immunogens for HIV-1 subtype C. Virology, 352(2), 438-449. https://doi.org/10.1016/j.virol.2006.05.011

Ancestral and consensus envelope immunogens for HIV-1 subtype C. / Kothe, Denise L.; Li, Yingying; Decker, Julie M.; Bibollet-Ruche, Frederic; Zammit, Kenneth P.; Salazar, Maria G.; Chen, Yalu; Weng, Zhiping; Weaver, Eric A; Gao, Feng; Haynes, Barton F.; Shaw, George M.; Korber, Bette T.M.; Hahn, Beatrice H.

In: Virology, Vol. 352, No. 2, 01.09.2006, p. 438-449.

Research output: Contribution to journalArticle

Kothe, DL, Li, Y, Decker, JM, Bibollet-Ruche, F, Zammit, KP, Salazar, MG, Chen, Y, Weng, Z, Weaver, EA, Gao, F, Haynes, BF, Shaw, GM, Korber, BTM & Hahn, BH 2006, 'Ancestral and consensus envelope immunogens for HIV-1 subtype C', Virology, vol. 352, no. 2, pp. 438-449. https://doi.org/10.1016/j.virol.2006.05.011
Kothe DL, Li Y, Decker JM, Bibollet-Ruche F, Zammit KP, Salazar MG et al. Ancestral and consensus envelope immunogens for HIV-1 subtype C. Virology. 2006 Sep 1;352(2):438-449. https://doi.org/10.1016/j.virol.2006.05.011
Kothe, Denise L. ; Li, Yingying ; Decker, Julie M. ; Bibollet-Ruche, Frederic ; Zammit, Kenneth P. ; Salazar, Maria G. ; Chen, Yalu ; Weng, Zhiping ; Weaver, Eric A ; Gao, Feng ; Haynes, Barton F. ; Shaw, George M. ; Korber, Bette T.M. ; Hahn, Beatrice H. / Ancestral and consensus envelope immunogens for HIV-1 subtype C. In: Virology. 2006 ; Vol. 352, No. 2. pp. 438-449.
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