In the pursuit of an effective HIV vaccine, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health, have conducted a study that sheds light on the crucial role of immune cells known as CD8+ T cells in protecting individuals from acquiring HIV.
Published in the journal Science, the study draws comparisons between the immune system responses of participants in past HIV vaccine trials and individuals with HIV who naturally control the virus without antiretroviral therapy (ART), commonly referred to as “long-term non-progressors” or “elite controllers” (LTNPs/ECs).
HIV enters the body and begins damaging the immune system by integrating into CD4+ T cells, which are white blood cells responsible for coordinating the immune response. In most individuals, HIV continues to replicate and harm CD4+ T cells unless controlled by ART. However, LTNPs/ECs exhibit a unique immune response where CD8+ T cells are activated promptly to recognize and destroy CD4+ cells infected with HIV, effectively suppressing the virus in their blood.
The primary goal of an effective HIV vaccine is to induce durable protective immunity or, if initial defenses are breached, to help control HIV in the body over the long term, similar to the natural response observed in LTNPs/ECs. Despite numerous attempts to design preventive HIV vaccines that stimulate CD8+ T-cell activity, previous candidates did not prevent HIV acquisition or control viral replication in clinical trials. Addressing this challenge has become a scientific priority in HIV vaccine research.
Scientists from the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation and their collaborators designed this study to understand the specific CD8+ T-cell functions that were lacking in previous HIV vaccine recipients. They compared laboratory samples from past HIV vaccine study participants with those from LTNPs/ECs. While both groups generated large numbers of CD8+ T cells recognizing HIV, the CD8+ T cells of vaccine recipients failed to deliver the proteins needed to destroy HIV-infected CD4+ T cells, unlike those of LTNPs/ECs.
Further investigation revealed that this impaired response was linked to reduced sensitivity to HIV in the T-cell receptors of vaccine recipients—the part of a CD8+ T cell responsible for detecting a CD4+ T cell with HIV. This reduced sensitivity indicates that the vaccine candidates from previous studies did not adequately stimulate the maturation of CD8+ T cells to recognize, reach, and destroy all CD4+ T cells with HIV in the body.
The study suggests that future HIV vaccine candidates might be more successful if they include additional doses or persist longer in the body to further stimulate the immune system. The authors propose that evaluating the potential of an HIV vaccine should involve measuring its impact on CD8+ T-cell function and sensitivity, in addition to assessing the quantity of CD8+ T cells generated, which has been the traditional practice.
These findings contribute to the ongoing research by the HIV-Specific Immunity Section of NIAID’s Laboratory of Immunoregulation to deepen our understanding of the immune response to HIV. The insights gained from this work may inform the design and development of future preventive and therapeutic HIV vaccines, as well as HIV immunotherapy approaches.
News Reference
National Institute of Health, https://www.nih.gov/news-events/news-releases/nih-research-identifies-opportunities-improve-future-hiv-vaccine-candidates.
