Fitness Constraints on Immune Escape from HIV: Implications of Envelope as a Target for Both HIV-Specific T Cells and Antibody

Sterilising immunity against HIV-1 infection, whilst ideal, appears an unrealistic vaccination goal in the short term. More achievable is slowing the progression to disease and decreasing transmission by mounting strong T cell and neutralising antibody responses to maintain low viral loads. However, in both acute and chronic infection, mutant virus is selected to escape both arms of the adaptive immune system. Each mutation away from wildtype virus likely incurs at least some reduction in replicative capacity ("fitness") of the virus. Rapid reversion to wildtype of some immune escape mutations upon transmission, suggests fitness costs may be significant. HIV-1 Envelope is unique in that it is subject to both neutralising antibody and cell-mediated immune responses. Although Envelope is variable between strains, considerable serial pressure and mutational escape from both neutralising antibody and cytotoxic T lymphocyte attack may result in impaired structure and function. This could ultimately be exploited in HIV vaccine design.