HIVACAT identifies candidate to HIV vaccine and initiates animal experimentation

• HIVACAT has identified several protein fragments with high potential to stimulate an effective immune response against HIV.
• This finding has required studies in over 1,000 patients and has allowed HIVACAT to move on to the third stage in the development of this vaccine. Satisfactory tests currently carried out in mice show that the immune response is activated by this candidate. Should results prove successful, HIVACAT investigators will further proceed to candidate optimization and initiate human subject research.
• HIVACAT, devoted to vaccine development research, is integrated by the IrsiCaixa Institute for AIDS Research and by the Infectious Disease and AIDS Service of the Hospital Clínic of Barcelona - IDIBAPS, in coordination with Esteve, with “la Caixa” Benevolent Fund, and with the Health and Economy and Knowledge Departments of the Generalitat de Catalunya.

In the course of HIVACAT’s III Annual Symposium held today at CaixaForum and organized by the HIVACAT consortium, participated by the IrsiCaixa Institute for AIDS Research and by the Infectious Disease and AIDS Service of the Hospital Clínic of Barcelona - IDIBAPS, in coordination with Esteve, with “la Caixa” Benevolent Fund, and with the Health and Economy and Knowledge Departments of the Generalitat de Catalunya, IrsiCaixa has announced successful identification of candidates to a possible HIV vaccine, and has produced these in the laboratory. The third of the six stages involved in the development of this vaccine is thus initiated, and is to include animal experimentation.

Identified candidates are HIV protein fragments with high potential to stimulate an immune response against this virus and to simultaneously create a lifelong memory to maintain this response against possible future infections. In addition to constituting preventive vaccine candidates, these fragments could also be part of a therapeutic vaccine able to help virus carriers fight and control the infection in order to prevent AIDS onset without requiring lifelong antiretroviral therapy.

If animal tests prove successful, the three stages of human subject research, which are indispensable to launch any new drug onto the market, can be initiated.

Given that previous studies have already shown that an HIV vaccine is effective only if able to stimulate the antibody-mediated and the T cell-mediated immune responses, the candidates presented today by IrsiCaixa are designed to stimulate both these two types of responses.

HIVACAT investigators, however, stress the fact that achieving all stages involves a long and costly process, beset with obstacles.

Candidates to stimulate antibody production
IrsiCaixa’s candidate to stimulate antibody production is a fragment of a protein found in the HIV membrane. While this protein had already proved to stimulate an effective immune response against HIV in primates, it was not effective enough to trigger a response likely to protect humans against infection. IrsiCaixa has identified one fragment of this protein, called GP41, which could be a good immune response stimulator. Importantly, this fragment has never been tested before on account of it being “concealed” under other fragments of the same protein which prevented it from being exposed and thus foster an immune response.

Our investigators have synthesized this protein fragment in the laboratory and have also found that it is recognized in vitro by the antibodies that block the infection. Previous candidates, which failed to stimulate the desired immune response, were injected as a solution in mice. According to IrsiCaixa’s investigators, this could have modified the nature of the proteins and hindered the immune response. Instead of a solution, genetic engineering was used to insert the candidate identified by IrsiCaixa onto the membrane of a noninfectious virus. According to investigator and study director Julià Blanco, “presenting the protein to the immune system onto the membrane allows maintaining a structure that is much more similar to the original one, and this could stimulate the immune response more effectively”.

Candidates to stimulate T cell-mediated immune response
HIVACAT’s bet is to complement the vaccine with other protein fragments that stimulate the immune response mediated by white blood cells known as T lymphocytes, or T cells, which will simultaneously contribute to strengthen the response mediated by the action of the “concealed” fragment. Specifically, these fragments will stimulate the production of two types of T lymphocytes: cytotoxic T lymphocytes, responsible for recognizing and killing infected cells, and T4 lymphocytes, which segregate a substance that activates cytotoxic T lymphocytes and renders these more efficient, in addition to stimulating antibody production already stimulated by the “concealed” fragment.

In order to identify these other candidates that stimulate T cell immune response, IrsiCaixa’s research team led by Christian Brander, in collaboration with other international research centers, studied which specific proteins did foster a good immune response in 1,000 HIV-infected subjects. This study allowed identifying 46 viral protein fragments that stimulated responses in the subjects who best controlled their infection in a natural way. Hence, these 46 fragments have been identified by means of a rational design –i.e. the experimental data of these 1,000 subjects– and introduced in one single linear sequence as a part of HIVACAT’s vaccine to stimulate T cell-mediated immune response.

Vaccine optimization
Should the studies performed in mice and humans evidence that HIVACAT’s candidates do stimulate an effective immune response, candidate optimization will be performed by HIVACAT using technology made available by investigator Eloïsa Yuste, from Hospital Clínic of Barcelona – IDIBAPS, who specializes in protein fragment optimization intended to improve immune response stimulation efficiency. HIVACAT also expects to greatly optimize vaccine action by means of a novel treatment whereby the injection of a hormone would improve treatment efficacy in HIV-infected patients. This hormone was identified as a growth hormone, which allows recovery of the very weakened immune system found in subjects such as HIV+ patients, and which does so in a way that vaccines previously failing to activate the immune system would gain efficacy. HIVACAT is also working on the design of other vaccine candidates that have not yet reached the mice study phase, and also has a candidate to therapeutic vaccine now undergoing the clinical trial phase.

In parallel, CaixaForum will host the 8th International Retroviral NC Symposium, to be held between 18th and 21st September. This Symposium is supported by BIOCAT and by the International Center for Science Debate, and is sponsored by “la Caixa” Benevolent Fund, HIVACAT, the Lluita Contra la Sida Foundation, SAIC-Frederick, ANRS, the Office for AIDS Research, and the Ramón Areces Foundation.