Study suggests ways to improve future HIV vaccine candidates

HIV cell

An effective HIV vaccine may need to prompt strong responses from CD8+ T cells to protect people from acquiring HIV, according to a study from the National Institute of Allergy and Infectious Diseases (NIAID).

The researchers drew comparisons between the immune system activity of past HIV vaccine study participants and people with HIV who naturally keep the virus from replicating even in the absence of antiretroviral therapy (ART), called ‘long-term non-progressors’ or ‘elite controllers’ (LTNPs/ECs).

HIV damages the immune system by inserting itself into CD4+ T cells. Among LTNPs/ECs, the immune system appears to promptly recognise CD4+ cells with HIV and activate other immune cells called CD8+ T cells, which destroy CD4+ cells with HIV.

Although several preventive HIV vaccine candidates have been designed to stimulate CD8+ T-cell activity, they did not prevent HIV acquisition or control viral replication in clinical trials.

Reduced sensitivity to HIV

Scientists in the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation and colleagues found that both HIV vaccine recipients and LTNPs/ECs generated large numbers of CD8+ T cells that recognised HIV. However, unlike the CD8+ T cells of LTNPs/ECs, HIV vaccine recipients’ CD8+ T cells failed to deliver the proteins necessary to destroy HIV-infected CD4+ T cells.

Further tests revealed that this dampened response was due to reduced sensitivity to HIV of vaccine recipients’ T-cell receptors. This suggests the vaccine candidates from several prior studies did not sufficiently stimulate the maturation of CD8+ T cells to recognise, reach and destroy all CD4+ T cells with HIV in a person’s body.

The study indicates that future HIV vaccine candidates may be more successful if they include additional doses or persist longer in the body to further stimulate the immune system. The researchers also say the potential of an HIV vaccine might be better judged by measuring how it affects CD8+ T-cell function and sensitivity rather than just the number of CD8+ T cells generated.

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