Justification for the inclusion of Gag in HIV vaccine candidates

It is widely accepted that effective human immunodeficiency virus (HIV) vaccines need to elicit a range of responses, including neutralising antibodies and T-cells. In natural HIV infections, immune responses to Gag are associated with lower viral load in infected individuals, and these responses can be measured against infected cells before the replication of HIV. Priming immune responses to Gag with DNA or recombinant Bacillus Calmette-Guérin (BCG) vaccines, and boosting with Gag virus-like particles as subunit vaccines or Gag produced in vivo by other vaccine vectors, elicits high-magnitude, broad polyfunctional responses, with memory T-cell responses appropriate for virus control. This review provides justification for the inclusion of HIV Gag in vaccine regimens, either as a transgene expressing protein that may assemble to form budded particles, or as purified virus-like particles. Possible benefits would include early control via CD8(+) T-cells at the site of infection, control of spread from the entry portal, and control of viraemia if infection is established.