Transfer of the ability of HIV-1 Tat to raise an adjuvant-free humoral immune response to unrelated antigens

Vaccine. 2012 Apr 16;30(18):2859-68. doi: 10.1016/j.vaccine.2012.02.042. Epub 2012 Feb 29.

Abstract

The HIV-1 Tat protein is able to raise a humoral immune response in the absence of adjuvant. Here, we investigated whether this property can be transferred to unrelated antigens. We first observed that Tat self-adjuvanticity is a T cell-dependent phenomenon in which a Th2 profile predominates. Then, we showed that the determinant governing the property is located in the region 1-57 of Tat and that fragment Tat1-57 can make two unrelated model antigens immunogenic in the absence of adjuvant. We found a Th2 pattern of immune response for both antigens, suggesting that Tat1-57 mediates this response. Next, we showed that, although less efficient than Tat1-57, the Tat37-57 fragment suffices to transfer the adjuvant property to other antigens. We also observed that preservation of cysteine 37 is absolutely required for the transfer, suggesting the role of disulphide-mediated dimerization in the transfer of the adjuvant property. Our observations suggest that for various antigens, the use of Tat37-57 or Tat1-57 or Tat22-57C(22-34)A might represent an alternative to adjuvants in humans, thereby opening up new perspectives in vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / genetics
  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Antigens / immunology*
  • DNA Mutational Analysis
  • Female
  • Immunity, Humoral*
  • Mice
  • Mice, Inbred BALB C
  • Structure-Activity Relationship
  • Th2 Cells / immunology
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • tat Gene Products, Human Immunodeficiency Virus