Innate Immunity to HIV

Vaccines represent one of the most successful public health interventions of the last century. But despite many attempts, only one HIV vaccine efficacy trial has shown a mildly positive result.  While there are many reasons to explain the difficulties of realizing an effective HIV vaccine, the most obvious explanation relates to the biology of HIV infection.

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Key Points

• HIV infects the cells of the immune system such as T cells, monocytes and macrophages. Whereas adaptive immune responses during HIV infection have been extensively studied, knowledge regarding the innate immune response to HIV is still scarce.
• Very early (days) into HIV infection, innate responses can play an important role in preventing mucosal transmission before HIV infection is established.
• Intracellular restriction of retroviruses has evolved in primates, and HIV has also evolved mechanisms to overcome this restriction and use the host cellular machinery to its advantage.
• Innate immune responses restrict the viral replication and activate adaptive immunity to fight the virus; however the same responses also increase the target cell availability and thereby facilitate further viral replication and contribute to disease progression. Dendritic cell, NK cell, and cytokine responses are prominent in acute HIV infection.
• Chronic innate immune activation is a major contributor of HIV immunopathogenesis and progression to AIDS.
• The failure of previous HIV-1 vaccine trials to induce B and T cell immunity emphasizes the need to look beyond adaptive immunity in order to gain control of HIV infection.  It is becoming evident that both innate and adaptive arms of the immune system need to be harnessed in order to develop a successful HIV vaccine.

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