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Clínic Barcelona

Gene Therapy Protects Simians Against Infection by the AIDS Virus

A study carried out in the United States has managed to introduce into the muscle cells of macaque monkeys the DNA necessary to produce an antibody-like molecule that is effective against SIV, the virus that causes AIDS in simians. The strategy consists of injecting an adenovirus that introduces the necessary DNA sequence into the nucleus of the muscle cells of the macaques. The researcher, Eloísa Yuste is one of the authors of the study and currently works on the IDIBAPS-Hospital Clínic team led by Dr. Josep Maria Gatell, co-director of HIVACAT(*).

Obtaining a preventive vaccine effective against the AIDS virus is one of the main challenges facing modern medicine. The candidates tested to date have shown disappointing results, making innovative approaches that open new lines of research necessary. A study published in Nature Medicine in its next issue presents the encouraging results obtained using a radically new strategy: introducing into the muscle cells of macaques DNA that codes for an antibody-like molecule that is effective against the simian immunodeficiency virus (SIV). The study was led by the Children’s Hospital of Philadelphia of the University of Pennsylvania, the Research Institute at Nationwide Children’s Hospital, Columbus, and the New England Primate Research Center of Harvard University. One of the authors of the study is Dr. Eloísa Yuste, currently a Ramon y Cajal researcher with the IDIBAPS-Hospital Clínic Infectious Diseases and AIDS team, led by Dr. Josep Maria Gatell, who is also a professor at the UB Department of Medicine. Since April 2008, she has been part of the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), but her role in the study took place during her last 6 months as a researcher at Harvard University. Her new research takes place in the framework of the HIVACAT program(*), co-directed by Dr. Gatell, with Dr. Bonaventura Clotet of IrsiCaixa.

From left to right: Dr. Alberto Merino, Dr. Maximiliano Medina and Dr. Eloísa Yuste Vaccine candidates have been plentiful since the AIDS virus was discovered 25 years ago. Some of them have reached the first stage of development in humans but with disappointing results. To date, traditional vaccines have not been able to provide protection against infection with the virus or effectively reduce its replication after infection. In simians, it has been possible to protect against infection by periodically injecting antibodies, but this is an inviable solution in clinical practice as injections must be given every few weeks. Production of antibodies has only been achieved in mice by implanting encapsulated fibroblasts with DNA that contains information coding for antibodies that are effective against the virus. Again, this strategy would appear not to be viable in clinical practice and, furthermore, the differences between immune systems mean that it is difficult to extrapolate the results obtained with these animal models to humans.

The new proposal consists of injecting an adenovirus containing genetic information that codes for an antibody that is effective against SIV into the muscle cells of 9 macaques. Good results were obtained in mice in previous studies and this study represents a considerable advance for its possible application in humans. Adenoviruses are small viruses that are used as vectors for transferring genetic information to the cells they infect. The 9 macaques were separated into groups of 3 and each group received an adenovirus loaded with the DNA necessary to express a different antibody effective against SIV. In the following weeks, the researchers studied the evolution of the antibodies in the serum of the monkeys and showed that their muscle cells were producing it. After 4 weeks, the 9 immunoprotected macaques were infected with a common form of SIV. None of them developed the disease after a year of follow-up and 6 of them showed no trace of infection.

The results open up a new line of research that could introduce gene therapy as an alternative in the fight against the propagation of the AIDS virus. There are still many questions to be answered, such as the level of protection the technique provides against infection via body fluids, as the antibodies circulating in the blood may not reach optimum concentrations in areas such as the epithelium of the vagina. Nevertheless, the results obtained with vaccines such as that against the human papilloma virus indicate that sustained production of antibodies reaching the blood would also provide protection against sexual transmission. It will also be necessary to find antibodies that are as effective against the different strains of HIV as those used in this study against SIV. The research in the American centers responsible for the article and that of the IDIBAPS team, which Dr. Eloísa Yuste has joined, will look for answers to the remaining questions and will continue to work on this innovative strategy.

(*) HIVACAT is a joint program of Hospital Clínic, Barcelona and IrsiCaixa to research vaccines against HIV. This initiative is funded by Fundació la Caixa, Laboratoris Esteve and the Catalan Ministries of Health and Universities.