IrsiCaixa participates in an $18M international project to develop a preventive HIV vaccine

IrsiCaixa —a center promoted by the ”la Caixa” Foundation and the Department of Health of the Generalitat of Catalonia— has recently signed an agreement to join Opti-FliP (Optimal T-cell support for HIV neutralizing antibody induction to fusion peptide-inclusive regimens), an international project aimed at developing a preventive HIV vaccine. With $18 million in funding from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), the project adopts an innovative approach that combines two key components of the immune system: antibodies and T cells.

Opti-FliP joins the three NIH-funded projects currently being carried out by IrsiCaixa, all focused on HIV research in the areas of vaccines, cure strategies, and big data analysis. “We are aware of the uncertain context surrounding us, but receiving this funding demonstrates that our project continues to move forward and highlights the importance of continuing research in this direction”, says Christian Brander, ICREA researcher at IrsiCaixa and co-principal investigator of Opti-FliP.

Over the next five years, researchers at IrsiCaixa, with a budget of $2 million, will lead one of the three main pillars of the project. Their goal is to identify parts of HIV that, when incorporated into a vaccine, can enhance a specific type of T cell needed to generate more effective antibodies capable of blocking infection. All of this is aimed at advancing toward a prevention strategy accessible to everyone.

“The goal of a preventive HIV vaccine is to prevent the virus from entering the body and establishing a permanent infection. To achieve this, we need to generate neutralizing antibodies, which are responsible for blocking the virus from entering target cells, specifically CD4+ T cells”, explains Brander. “In this project, we seek to redefine the paradigms that have guided the development of preventive vaccines over the past 40 years, with the aim of optimizing both the quantity and quality of a specific type of T cell and enhancing its ability to strengthen the action of these antibodies”, he adds.

Overcoming the challenges of current HIV vaccines

One of the main obstacles in developing HIV vaccines is the low production of neutralizing antibodies. Opti-FliP aims to address this issue by strengthening the response of a specific type of T cell: follicular T cells, which play a crucial role in antibody production by B cells.

“At IrsiCaixa, we seek to enhance follicular T cells, which are key for B cells to produce more effective antibodies against HIV. Until now, only CD4+ follicular T cells had been studied, but activating them posed a risk since they can become infected and serve as virus reservoirs”, explains Àlex Olvera, researcher at IrsiCaixa and collaborator on Opti-FliP. “In a recent study, we discovered the existence of CD8+ follicular T cells, which perform the same function without the risk of infection. This finding opens new opportunities for developing safer and more effective HIV strategies”, he adds.

To enhance the effectiveness of CD8+ follicular T cells, Opti-FliP will also investigate the use of IL-10 inhibitors, a molecule that suppresses the immune response. By blocking its action, the research team aims to strengthen the activation of T and B cells, thereby improving the immune response to the vaccine.

“A key aspect is that, unlike other vaccination strategies that use the complete viral envelope, we will explore methods to stimulate the production of neutralizing antibodies specifically targeting the fusion peptide, a critical part of the HIV envelope. This approach would allow us to attack a region of HIV that has so far been largely unexplored as a target”, explains Cristina Peligero, researcher at IrsiCaixa and collaborator on Opti-FliP.

The ultimate goal is to design an immunogen that meets these characteristics. To achieve this, samples will be analyzed from people living with HIV who are considered elite neutralizers, as they naturally generate antibodies with a high capacity to neutralize the virus from the early stages of infection. These individuals will be identified in Spain and South Africa, allowing researchers to study immune responses in different population contexts and against various HIV variants.

Finally, the results obtained will be validated in preclinical models, enabling an assessment of this strategy’s feasibility before its application in clinical trials.

An international collaboration to redefine HIV prevention and its future

Opti-FliP is a global effort that brings together Christian Brander, co-principal investigator of the project at IrsiCaixa, Dennis Hartigan-O'Connor and Ellen Sparger, co-principal investigators of the project at the University of California in Davis, Penny Moore, co-principal investigator of the project at the University of Witwatersrand, and Bryce Chackerian, project collaborator at the University of New Mexico. This collaboration will allow for the combination of different perspectives and methodologies to advance the development of an effective vaccine.

"Despite advances in preventive treatments, adherence remains a challenge. In addition to the current uncertainties regarding global access to antiretroviral treatment, this highlights that a preventive vaccine will be the only accessible and sustainable solution to combat HIV", concludes Brander.