Ancestral and consensus envelope immunogens for HIV-1 subtype C
| Autor: | Julie M. Decker, Frederic Bibollet-Ruche, Kenneth P. Zammit, Zhiping Weng, Bette T. Korber, Denise Kothe, George M. Shaw, Beatrice H. Hahn, Yalu Chen, Barton F. Haynes, Yingying Li, Maria G. Salazar, Feng Gao, Eric A. Weaver |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
HIV Antigens
T cell viruses Guinea Pigs Molecular Sequence Data Heterologous HIV Infections Cross Reactions HIV Antibodies Genes env Evolution Molecular 03 medical and health sciences chemistry.chemical_compound Mice Immune system HIV-1 genetic variation Antigen Neutralization Tests Centralized HIV-1 immunogens Virology Consensus Sequence medicine Animals Humans Amino Acid Sequence Gene Phylogeny 030304 developmental biology chemistry.chemical_classification AIDS Vaccines 0303 health sciences Mice Inbred BALB C biology Sequence Homology Amino Acid 030306 microbiology virus diseases Gene Products env Subtype C 3. Good health medicine.anatomical_structure chemistry biology.protein HIV-1 Antibody HIV-1 envelope glycoprotein Glycoprotein DNA |
| Zdroj: | Virology. 352(2):438-449 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2006.05.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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