The HTI vaccine of AELIX Therapeutics, a spin-off of HIVACAT, shows in a Phase I/IIa clinical trial that 40% of the participants who received the vaccine have better control of the virus when the treatment is temporarily withdrawn
Currently, people living with HIV have to take daily antiretroviral treatment because their immune system is not able to control the virus by itself. Now, the results of HTI therapeutic HIV vaccine clinical trial, promoted by AELIX Therapeutics, show that this vaccine can educate the immune system to improve the response against the virus. To assess efficacy, participants temporarily interrupted their antiretroviral treatment after vaccine administration and were weekly monitored during 6 months. The study has proved the safety of the vaccine and has shown that the immune response generated by the participants is directly related to the time they have remained untreated. In particular, among the participants without favourable genetic background predisposing to spontaneous HIV control, the 40% of vaccinated participants were able to remain off treatment during the 6 months of the study. In contrast, in the group placebo, all but one participant had to restart treatment before 12 weeks of treatment interruption.
This vaccine, designed at the IrsiCaixa AIDS Research Institute, a center promoted by "la Caixa" Foundation and the Department of Health of the Generalitat de Catalunya, paves the way for new cure strategies in combination with other vaccines, immunotherapies or drugs. The study, conducted at the Germans Trias i Pujol Hospital by the Fight AIDS and Infectious Diseases Foundation and IrsiCaixa, has counted with the collaboration of Oxford and BCN Checkpoint, and its results are presented today at the Conference on Retroviruses and Opportunistic Infections 2021 (CROI), one of the world’s leading conferences in the field of HIV/AIDS.
HIV remains dormant in cells of the immune system in the form of a viral reservoir. This is why, when antiretroviral treatment is interrupted, the virus emerges from these reservoirs within a few weeks and, since the immune system of people living with HIV infection usually cannot spontaneously control HIV, the amount of virus in the blood increases rapidly. However, there is a very small percentage of people who are able to generate a very potent immune response against the virus and have better control of the infection. "We studied which parts of the virus are attacked by the immune system of these people so that we can simulate their response against the virus artificially. This is how we identified vulnerable parts of the virus and designed the HTI immunogen, the basis of the HTI vaccine," explains Beatriz Mothe, associate researcher at IrsiCaixa and co-inventor of the HTI vaccine together with Christian Brander and Anuska Llano. "The results obtained in the laboratory and in animal models were promising, so we decided to push forward the development of the vaccines and test them in clinical trials," says Brander, principal investigator at IrsiCaixa and scientific director of AELIX Therapeutics, the Barcelona-based biotech company leading the clinical development of the HTI vaccine. Mothe, together with José Moltó, both physicians from the Infectious Diseases Service at the Hospital Germans Trias and FLSida, led the study. "The follow-up of the patients lasted almost 3 years and was completed during the health emergency generated by COVID-19, a fact that represented a real challenge both for the participants, the researchers and the promoter AELIX Therapeutics," explains Moltó.
Educating the immune system to better control the virus
The clinical trial, named AELIX-002, recruited people with a recent HIV diagnostic and early-treated, thanks to the circuit jointly implemented by BCN Checkpoint and FLSida. This inclusion criteria was essential, as these patients have a stronger immune system and a smaller viral reservoir than people with late diagnosis.
Participants received two rounds of vaccination and, later, they temporarily interrupted their antiretroviral treatment. During this second phase of the trial, participants’ viral load was monitored weekly. Among the 45 participants who started the study, 41 reached the interruption phase and, of these, 26 received the vaccine and 15 received placebo, something that neither the patients nor the doctors knew until the study was completed. The researchers found that 8 participants (40%) without any genetic background predisposing to spontaneous HIV control were able to remain untreated for the 6 months of the study, compared to the placebo group, in which every participant but one had to restart the antiretroviral treatment. "Despite the fact that all the participants had detectable virus in their blood at some point, these results are a first proof of concept that we can modify the immune response against the virus to be stronger and better able to control the infection," says Mothe.
97% of vaccinated participants have, at least, doubled the specific immune response against the HTI immunogen, the vulnerable parts of the virus presented by the vaccine. In fact, magnitude of specific response against the immunogen correlated with the time vaccinated participants were able to remain off treatment.
Tackling the virus with combined strategies
The current data suggest that HTI vaccines may be a key building block for combined cure strategies and reinforce AELIX Therapeutics' ongoing lines of research. Next steps include understanding how to increase the immune response generated and achieving a larger number of participants to remain at low viral loads without treatment. "We are currently initiating new studies that combine the use of the therapeutic HTI vaccine with drugs that can reverse the latency of the viral reservoir and further boost the immune response against the virus," explains José Luis Cabero, Chief Executive Officer at AELIX Therapeutics. The AELIX-002 study has been developed under a collaborative agreement between AELIX Therapeutics and the pharmaceutical company Gilead Sciences. A combination of HTI vaccines with Gilead's drug vesatolimod is currently being evaluated in the clinical trial identified as NCT04364035.
Finding an effective strategy to replace daily treatment would improve the quality of life of people living with HIV, its associated stigma and the potential toxicities of long-term antiretroviral treatments.