The mutable vaccine for mutable viruses

Immunotherapy. 2017 Jun;9(8):659-667. doi: 10.2217/imt-2017-0030.

Abstract

Mutable viruses, such as HIV, pose difficult obstacles to prevention and/or control by vaccination. Mutable viruses rapidly diversify in populations and in individuals, impeding development of effective vaccines. We devised the 'mutable vaccine' to appropriate the properties of mutable viruses that undermine conventional strategies. The vaccine consists of a DNA construct encoding viral antigen and regulatory sequences that upon delivery to B cells target the enzymatic apparatus of 'somatic hypermutation' causing the construct to mutate one million-times baseline rates and allowing production and presentation of antigen variants. We postulate the mutable vaccine might thus anticipate diversification of mutable viruses, allowing direct control or slowing of evolution. Initial work presented here should encourage consideration of this novel approach.

Keywords: B cell; HIV; antigen; escape variant; mutable virus; somatic hypermutation; vaccine; viral evolution; virus.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines* / genetics
  • AIDS Vaccines* / immunology
  • AIDS Vaccines* / therapeutic use
  • Animals
  • Antigens, Viral* / genetics
  • Antigens, Viral* / immunology
  • B-Lymphocytes / immunology
  • HIV Infections* / genetics
  • HIV Infections* / immunology
  • HIV Infections* / therapy
  • HIV-1* / genetics
  • HIV-1* / immunology
  • Humans
  • Mutation*
  • Somatic Hypermutation, Immunoglobulin / immunology
  • Vaccines, DNA* / genetics
  • Vaccines, DNA* / immunology
  • Vaccines, DNA* / therapeutic use

Substances

  • AIDS Vaccines
  • Antigens, Viral
  • Vaccines, DNA