25 years of research: a story in between pandemics, from AIDS to COVID-19

In 1995, the AIDS pandemic was wreaking havoc around the world, with more than 2 million people dying each year from the disease and its consequences. Aware of the importance of finding a solution, IrsiCaixa was inaugurated thanks to the support of "la Caixa" Foundation and the Department of Health of the Generalitat de Catalunya. 25 years later, and having managed to make the daily lives of people with HIV the same as those of the rest of the population, new challenges are emerging.

"IrsiCaixa has become a world reference in HIV research, and "la Caixa" Foundation did not hesitate to support it from the beginning in order to respond to the pandemic in which society was immersed in the nineties. A quarter of a century later, a new virus has appeared, the SARS-CoV-2, which has highlighted, more than ever, that the commitment to research is crucial for facing the challenges of today's and tomorrow's health, and is a key element for the well-being and health of the society," explains Àngel Font, Corporate Director of Research and Strategy at "la Caixa" Foundation.

Climate change and globalisation have made the planet more vulnerable to emerging viruses and have given rise to the SARS-CoV-2 pandemic this 2020. The serious health emergency has required a rapid and immediate reaction from the scientific world, to which IrsiCaixa has been able to respond thanks to all the knowledge generated in the field of HIV and the immune system. Currently, IrsiCaixa is working non-stop on 26 research projects at COVID-19. These projects aim to develop a vaccine, search for effective treatments and design rapid tests to detect the disease. "We have once again experienced the horrible feeling of not being able to have treatments to cure or prevent a disease", explains Bonaventura Clotet, director of IrsiCaixa. "We needed the research to deal with SARS-CoV-2 and, fortunately, we now had the necessary tools, all we had to do was adapt them," he adds.

Today, HIV persists and by 2019, 1.7 million new HIV infections have occurred worldwide. "HIV is still a reality for many people. A reality, however, that has nothing to do with that of 1995," explains Clotet. The great progress made so far brings a possible cure closer every day. IrsiCaixa has seen and formed part of this evolution, with milestones such as the discovery of how HIV spreads through the body; the design of therapeutic and preventive vaccines which have promoted the creation of two spin-offs; and the coordination of the international consortium IciStem, which has succeeded in curing two cases of HIV through bone marrow transplantation. IrsiCaixa is now studying the virus' resistance to antiretroviral treatment, the efficacy of the therapeutic vaccine designed in the laboratory and how to eliminate the reservoir, the niche where the virus hides and the main obstacle to ending this disease.

In order to speed up research, scientific patronage has been key for IrsiCaixa, which has gone from an initial capital of 14 million pesetas (84,000 euros) to 7.5 million euros, thanks to the endowment sustained over time by "la Caixa" Foundation and the Generalitat de Catalunya, as well as to the securing of European funds.
 

HIV research today

Since the beginning of the HIV pandemic, research has changed a lot. There has been a shift from urgently seeking treatment in order to save the lives of people with the infection to aiming for a cure or complete eradication of the disease. IrsiCaixa has been part of this progress and has contributed with 1,011 scientific articles. During this time, the team has analysed more than 110,000 samples from almost 25,000 patients who have participated in clinical trials that have allowed researchers to better understand HIV infection and to search for therapeutic alternatives for those living with the infection. While the Institute began with seven staff members to fight AIDS, it now has 107 enthusiastic researchers and 60 external collaborators from around the world. This expansion has enabled the training of health professionals –with access to state-of-the-art experimental facilities– and representatives of the HIV-affected community, as well as students from secondary schools, high schools and colleges.

Although HIV/AIDS infection can now be considered a chronic disease, the goal now is to cure it; to ensure that people living with HIV do not need to take antiretroviral medication. "Designing a therapeutic HIV vaccine is a big challenge because, unlike SARS-CoV-2, it mutates a lot and evades the response of our immune system, which is gradually being depleted," explains Beatriz Mothe, researcher and coordinator of clinical trials for vaccines and immunotherapies. "We are currently carrying out two clinical trials sponsored by AELIX Therapeutics in order to evaluate the safety and efficacy of therapeutic vaccines that were designed at IrsiCaixa. The COVID-19 pandemic has posed a huge challenge in keeping the trials active but, with a lot of effort and motivation, we have managed to move forward with the projects," she adds.
 

Replicating preventive and therapeutic strategies

IrsiCaixa, together with the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS) and the Animal Health Research Center IRTA-CReSA, and thanks to the support of Grifols, has formed a consortium to develop a vaccine to generate defences against SARS-CoV-2 and its variants. "We have been able to use innovative platforms that we had previously designed for the preventive vaccine against HIV", explains Julià Blanco, principal investigator in charge of the project at IrsiCaixa. "We have two vaccine prototypes that generate neutralizing antibodies in the animal model. Now we have to see if these protect against infection and study how to move on to industrial production", he adds.

All preventive strategies, to be effective, must go together with early diagnosis and treatment of infections. In the case of HIV, during the early years of the pandemic when available antiretroviral drugs were significantly toxic, treatment was not initiated until the immune system began to show signs that it might be weakening. Fortunately, current treatments have been shown to have very little toxicity, improving the health status of all people living with HIV regardless of their immune status, while at the same time preventing transmission of the virus to others within weeks of starting treatment. "In the case of COVID-19, we should proceed in a similar way: we should do many tests and not wait until the person has pneumonia to treat it", claims Clotet.
 

Research on emerging viruses, a necessary commitment

More than a year ago, before the arrival of the COVID-19 pandemic, IrsiCaixa created a new research group dedicated to the study of new emerging diseases, such as Ebola. Now, the world has become involved in a new pandemic and the importance of investing in research in the field of emerging viruses has been highlighted. "Globalisation, and therefore the interconnection between the animal, human and environmental worlds, makes us increasingly vulnerable to potential emerging pathogens, such as viruses," explains Nuria Izquierdo-Useros, the leader of this new group. "These pathogens are conquering new geographical regions, compromising global health and generating serious consequences, such as pandemics," she adds. For this reason, IrsiCaixa has broadened its field of research and is committed to the "One Health" concept, that is, understanding health as an interactive sum of animal, environmental and human health.

At the same time, IrsiCaixa keeps working to achieve a cure for HIV infection and to improve the quality of life of people living with the virus, as well as to fight against the associated stigma. IrsiCaixa's expansion has led the institution to be able to explore new fields of research related to HIV, such as the study of the microbiome, ageing, cancer, neurodegenerative diseases and emerging pathogens. "There are many challenges that still lie ahead of us but, as always, we face them with strength and enthusiasm," concludes Clotet.