We are proud to share our laboratory’s role in a landmark clinical study published in Nature Communications, titled “Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial.” The AELIX-003 trial represents a significant step forward in the global effort to develop a functional cure for HIV. Synexa was directly involved in validating and executing the ELISpot assay used to evaluate the vaccine’s effectiveness in stimulating virus-specific immune responses.
About the AELIX-003 Study: A Milestone in Therapeutic Vaccination
The AELIX-003 study investigated whether a combination of therapeutic HIV vaccines, based on HTI (HIVACAT T-cell immunogen), and vesatolimod (VES), a Toll-like receptor 7 (TLR7) agonist, could boost the body’s ability to control HIV following treatment interruption. The vaccines, ChAdOx1.HTI and MVA.HTI, were administered to participants who had started antiretroviral therapy (ART) early in the course of infection. Following vaccination, participants underwent a 24-week analytical treatment interruption (ATI), during which they paused ART under close clinical monitoring to assess whether the vaccine-induced immune response could delay or suppress viral rebound.
The therapeutic strategy is rooted in the idea of enhancing the host’s immune system to recognise and control HIV replication without continuous ART. This approach could one day offer individuals living with HIV the possibility of long-term remission without daily medication.
Validating and Executing the ELISPOT Assay
Synexa validated and performed the ELISPOT assay, which measured the ability of T cells to produce interferon-gamma (IFN-γ) in response to HTI peptide stimulation. This assay was central to the immunogenicity analysis in the study, enabling researchers to quantify the frequency and magnitude of HTI-specific T cell responses induced by the vaccine regimen. We worked closely with the Aelix team to optimise and validate the assay conditions, ensuring that the data generated met regulatory and scientific standards.
Key Immunological Insights
The ELISpot results provided critical insights into the immune responses of trial participants. The data showed that the vaccine regimen successfully elicited strong and broad T cell responses targeting conserved regions of the HIV genome—areas less likely to mutate and escape immune detection. The ELISpot assay results played a pivotal role in demonstrating that participants who received the vaccine developed significantly higher HTI-specific responses compared to those who received a placebo.
From a safety standpoint, the study found that the vaccine and vesatolimod combination was well-tolerated, with only mild to moderate adverse events such as injection site pain, fever, and fatigue. Importantly, no serious adverse events related to the study treatment were reported. These safety outcomes are critical in the context of HIV cure research, where therapeutic interventions must not compromise the well-being of otherwise healthy individuals on effective ART.
Although all participants eventually experienced viral rebound after stopping ART, the study noted that a higher proportion of vaccinated individuals (33.3%) remained off ART for the full 24-week ATI period compared to the placebo group (23.5%). Notably, a post hoc analysis revealed that those individuals with stronger HTI-specific T cell responses exhibited a delay in viral rebound, underscoring the potential clinical relevance of these immune responses.
As efforts to develop a functional cure for HIV continue, studies like AELIX-003 provide essential lessons on how to safely and effectively harness the immune system to control viral replication. As future trials build on these findings, we look forward to continuing our contributions: bringing validated, high-sensitivity immunological assays such as the ELISpot assay which provide resolution of the T-cell arm of immunity—information that is critical for evaluating vaccine candidates like HTI.
To read more about the trial and its outcomes, you can access the full publication here:
https://www.nature.com/articles/s41467-025-57284-w
