Study Results Suggest New Opportunities to Improve Future HIV Vaccine Candidates

According to new research published in Science, an effective HIV vaccine may need to prompt strong responses from CD8+ T cells to protect people from acquiring HIV. The study findings demonstrate comparisons between the immune system activity of past HIV study participants and those with HIV who naturally keep the virus from replicating itself, even when antiretroviral (ART) is not in use. The individuals who naturally prevent HIV from replicating are often called long-term non-progressors, or elite controllers (LTNPs/ECs).

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HIV damages the immune system by inserting itself in CD4+ T cells—white blood cells that help coordinate immune responses to pathogens—once it enters the body. In most individuals, HIV continues to replicate, damaging even more CD4+ T cells unless controlled by ART; however, among LTNPs/ECs, the immune system appears to recognize CD4+ cells with HIV and activate other immune cells, CD8+ T cells, to destroy the CD4+ cells with HIV, allowing the suppression of HIV in a person’s blood.

The goal of an effective HIV vaccine is to provide durable, protective immunity to HIV or to help control HIV in the body long-term if initial defenses are bypassed, which can happen with LTNPs/ECs. In addition, several preventive HIV vaccine candidates have been designed to stimulate CD8+ T cell activity; however, the candidates did not prevent the acquisition of HIV or control viral replication in clinical trials. Investigators note that understanding and addressing the lack of effect is a priority in HIV vaccine research.

To better understand which CD8+ T cell functions were lacking in previous HIV vaccine recipients, the investigators designed their study differently, comparing laboratory samples from previous HIV vaccine study participants with samples from LTNPs/ECs. The investigators determined that HIV vaccine recipients and LTNPs/ECs had both generated large amounts of CD8+ T cells that recognized HIV; however, unlike LTNPs/ECs, HIV vaccine recipients’ CD8+ T cells had failed to deliver the necessary proteins used to destroy HIV-infected CD4+ T cells with HIV.

Additional research suggests hindered responses are due to the reduced sensitivity to HIV of vaccine recipients’ T cell receptors, the part of a CD8+ T cell which detects whether there is HIV in CD4+ T cells. The lack of sensitivity suggests that the vaccine candidates from prior research did not sufficiently stimulate the maturation of CD8+ T cells to recognize, reach, and destroy all CD4+ T cells with HIV in a patient’s body.

According to the authors, the research suggests that future vaccine candidates can be more successful if additional doses are included or if doses persist longer in the body, further stimulating the immune system. Furthermore, the investigators also note that the potential of an HIV vaccine would potentially be better judged by them measurement of how CD8+ T cell function is affected, its sensitivity, and the number of generated CD8+ T cells. The findings gathered from the research can help in making steps toward future preventative and therapeutic HIV vaccine design and development, as well as HIV immunotherapies, according to the study authors.

Reference

National Institute of Allergy and Infectious Diseases. HIV research identifies opportunities to improve future HIV vaccine candidates. News release. December 14, 2023. Accessed December 18, 2023. https://www.eurekalert.org/news-releases/1011286

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