Vaccination with CTL epitopes that escape: an alternative approach to HIV vaccine development?

This article describes a novel approach to HIV vaccine design that is, as y et, unproven and still in preliminary development. In rhesus macaques infec ted with simian immunodeficiency virus (SIV), we have identified particular cellular immune responses that select for viral variants during primary in fection. We speculate that the detection of viral variants with altered ami no acids in CTL epitopes implies the successful clearance of cells harborin g wild-type virus. Here, we present our rationale suggesting why such poten t early CTL responses that exert an antiviral effect may be particularly at tractive targets for induction by candidate vaccines. Conventional wisdom s uggests that regions of the virus that are structurally and functionally im portant will generally be well-conserved both among clades and within an in fected host. Amino acid replacements within these well-conserved regions sh ould be difficult for the virus to accommodate. Therefore, these regions ar e traditionally considered ideal targets for vaccine induced immune respons es because they are refractory to CTL escape mutations. Many examples of th ese regions have been identified in both HIV-1 and SIVmac (J. Immunol. 162 (1999) 3727; J. Virol. 67 (1993) 438) and have been included in candidate v accine formulations. Human clinical trials testing these vaccines are curre ntly underway. Our proposed method of vaccination with CTL epitopes that es cape explores an alternative hypothesis. Rather than engendering responses to regions of the virus that do not escape, we reason that vaccination need s to accelerate the development of the initial immune responses that effect ively select for amino acid variants during acute infection. By examining C TL escape during the acute phase, we will identify CTL responses that the v irus cannot tolerate and incorporate these responses into vaccines. (C) 200 1 Elsevier Science BN. All rights reserved.