Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity

J Immunol. 2004 May 15;172(10):6290-7. doi: 10.4049/jimmunol.172.10.6290.


The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem is to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specific cellular immune responses elicited by rAd35-Gag. Low levels of cross-reactive Ad5/Ad35-specific CD4(+) T lymphocyte responses were observed, but were insufficient to suppress vaccine immunogenicity. These data demonstrate the potential utility of Ad35 as a candidate vaccine vector that is minimally suppressed by anti-Ad5 immunity. Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / classification
  • Adenoviridae / genetics*
  • Adenoviridae / immunology*
  • Adenoviridae Infections / immunology*
  • Adenoviridae Infections / prevention & control*
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dose-Response Relationship, Immunologic
  • Epitope Mapping / methods
  • Epitopes, T-Lymphocyte / blood
  • Gene Products, gag / administration & dosage
  • Gene Products, gag / blood
  • Gene Products, gag / immunology
  • Genetic Vectors
  • Immunity, Active
  • Immunization Schedule
  • Immunization, Secondary
  • Injections, Intramuscular
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Serotyping
  • Simian Immunodeficiency Virus / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology*


  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • Peptide Fragments
  • Vaccines, Synthetic
  • Viral Vaccines