The immune response during acute HIV-1 infection: clues for vaccine development

The early virological factors in HIV-1 infection, including transmission and the nature of the founder virus, can affect the time course of viraemia through the early peak to set point.The identification of patients within the first few weeks of HIV-1 infection has provided early evidence of immune system damage, including massive apoptosis of CD4+ T cells, which is associated with the presence of apoptotic microparticles and TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) in the blood, and damage to germinal centres in mucosal lymphoid tissues.The first innate immune responses include the appearance of acute-phase proteins, early cytokine storm and activation of natural killer (NK) cells. An innate immune response to HIV-1 can be damaging, however, as it can draw susceptible T cells to the infection foci.The first T cell response controls the founder virus by killing infected T cells. However, the T cell response also selects mutational changes in the founder virus, allowing immune evasion.The first B cell response consists of early immune complexes, followed by non-neutralizing antibodies against the founder virus and then the slow development of broadly acting neutralizing antibodies. Development of vaccines that rapidly induce broadly acting neutralizing antibodies might be beneficial in preventing HIV infection.Understanding the early events and immune responses is crucial to devising vaccine strategies that can improve the weak protection offered by current HIV vaccines that are being trialled, such as the RV144 (Thai) efficacy trial.