by A recent study conducted by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has shed light on potential improvements for future HIV vaccine candidates. The findings, published in Science, emphasize the need for an effective HIV vaccine to elicit strong responses from CD8+ T cells, a type of immune cell.
The research team compared the immune system activity of participants in past HIV vaccine studies with individuals who naturally control the virus without the need for antiretroviral therapy (ART), known as long-term non-progressors or elite controllers (LTNPs/ECs). HIV damages the immune system by targeting CD4+ T cells, which are essential in coordinating the immune response against pathogens. In most cases, HIV continues to replicate and harm CD4+ T cells unless suppressed by ART. However, LTNPs/ECs demonstrate a prompt recognition of CD4+ cells infected with HIV, leading to the activation of CD8+ T cells that destroy these infected cells and effectively suppress the virus.
The ultimate goal of an effective HIV vaccine is to provide durable protective immunity against the virus. Even if initial defenses are bypassed, the vaccine should be able to control HIV long-term, similar to the natural immunity observed in LTNPs/ECs. Although previous HIV vaccine candidates have aimed to stimulate CD8+ T-cell activity, they have failed to prevent HIV acquisition or control viral replication in clinical trials. Addressing this lack of efficacy is a crucial priority in HIV vaccine research.
To better comprehend the specific CD8+ T-cell functions lacking in past vaccine recipients, the scientists at NIAID’s Laboratory of Immunoregulation compared laboratory samples from previous HIV vaccine study participants with samples from LTNPs/ECs. Both groups exhibited a substantial presence of CD8+ T cells recognizing HIV. However, the CD8+ T cells of vaccine recipients did not produce the necessary proteins to destroy HIV-infected CD4+ T cells, unlike the CD8+ T cells of LTNPs/ECs.
Further investigation indicated that this diminished response in vaccine recipients was due to reduced sensitivity of their T-cell receptors, which detect CD4+ T cells with HIV. This reduced T-cell receptor sensitivity suggests that previous vaccine candidates did not adequately stimulate the maturation of CD8+ T cells to recognize and eliminate all HIV-infected CD4+ T cells in the body.
Based on these findings, the researchers suggest that future HIV vaccine candidates may be more effective if they include additional doses or persist longer within the body to further stimulate the immune system. Moreover, the potential of an HIV vaccine should be assessed based on its impact on CD8+ T-cell function and sensitivity, rather than solely on the number of CD8+ T cells generated.
These discoveries build on decades of research by the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation, contributing to a better understanding of the immune response to HIV. The insights gained from this work have the potential to inform the design and development of future preventive and therapeutic HIV vaccines, as well as HIV immunotherapy approaches.
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1. Source: Coherent Market Insights, Public sources, Desk research
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