Construction of a live-attenuated HIV-1 vaccine through genetic code expansion

Angew Chem Int Ed Engl. 2014 May 5;53(19):4867-71. doi: 10.1002/anie.201402092. Epub 2014 Apr 8.

Abstract

A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off in vitro.

Keywords: HIV-1 vaccine; attenuated vaccine; genetic code expansion; unnatural amino acid; virus engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology
  • HEK293 Cells
  • HIV-1 / pathogenicity
  • HIV-1 / physiology
  • Humans
  • Virulence

Substances

  • AIDS Vaccines