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Related Experiment Videos

Ancestral and consensus envelope immunogens for HIV-1 subtype C.

Denise L Kothe1, Yingying Li, Julie M Decker

  • 1Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Virology
|June 20, 2006
PubMed
Summary

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Ancestral and consensus HIV-1 subtype C env genes create functional envelope glycoproteins. These immunogens elicited broad humoral and cellular immune responses in animals, supporting their use in future AIDS vaccines.

Area of Science:

  • Virology
  • Immunology
  • Vaccine Development

Background:

  • Developing effective HIV-1 vaccines requires immunogens that elicit broad immune responses against diverse viral variants.
  • Centralized immunogens (ancestral or consensus) aim to minimize genetic distance to contemporary HIV-1 strains.
  • Experimental validation of the biological, antigenic, and immunogenic properties of these inferred gene products is crucial.

Purpose of the Study:

  • To construct and characterize the first full-length ancestral (AncC) and consensus (ConC) env genes of HIV-1 (group M) subtype C.
  • To assess the immunogenicity and breadth of immune responses elicited by AncC and ConC env DNA in animal models.

Main Methods:

  • Construction and codon-optimization of AncC and ConC env genes.
  • Expression and characterization of envelope glycoproteins, including incorporation into virions and infectivity.

Related Experiment Videos

  • Immunization of guinea pigs and mice with AncC and ConC env DNA.
  • Assessment of humoral responses (binding and neutralizing antibodies) and cellular responses (gamma interferon T cell responses).

    • Main Results:

    • AncC and ConC env genes expressed high levels of functional envelope glycoproteins that mediated CCR5-dependent infection and retained neutralizing epitopes.
    • Guinea pigs immunized with AncC and ConC env DNA showed high-titer binding antibodies and recognized more primary subtype C envelope glycoproteins compared to controls.
    • Mice immunized with AncC and ConC env DNA developed gamma interferon T cell responses recognizing overlapping peptides.
    • No significant homologous or heterologous neutralizing antibodies were observed in guinea pigs.

    Conclusions:

    • AncC and ConC env genes express functional envelope glycoproteins that are immunogenic in laboratory animals.
    • These centralized HIV-1 subtype C Env immunogens elicited humoral and cellular immune responses of comparable breadth and magnitude.
    • The findings support the continued evaluation of AncC and ConC env as potential components of future AIDS vaccines.