New advances towards an effective vaccine against HIV thanks to a sequential strategy

Scientists have made several advances in the design of a class of vaccines against HIV that could offer extensive protection against virusaccording to four new research works in which different methods have been developed to obtain broad-spectrum neutralizing antibodies.

The results of these still preliminary studies are published in the journals Science, Science Translational Medicine and Science Immunology, and all four describe new steps in a sequential vaccination strategy to obtain an effective candidate against the HIV virus.

The experiments were carried out in rhesus macaques and mice, and one of the proposals is in phase 1 of clinical trials. Among the authors are scientists from the American Scripps Research Institute, the University of Louisville and the University of California, San Diego.

The HIV epidemic has entered its fifth decade and the scientific community has dedicated time and resources to developing candidate vaccines against the virus.

However, health authorities still lack an effective and approved vaccine that induces broadly neutralizing antibodies, capable of neutralizing the most common circulating strains of HIV, recalls a summary from the Science group.

One solution is a process called germline selection, in which researchers use a series of proteins directed by the immune system (immunogens) to guide and ‘prepare’ to young B cells as they mature in places called germinal centers.

The goal is to induce cells to produce broadly neutralizing antibodies against HIV.

José Alcamí, director of the AIDS Immunopathology Unit of the Carlos III Health Institute, points out that the objective of any preventive vaccine is to induce the production of neutralizing antibodies by the immune system and usually the antigen used must include or be formed by the envelope or surface proteins of the virus.

It is these proteins that interact with the entry receptors in the cell, so their blocking by antibodies neutralizes the virus infection, tells Science Media Center Spain (SMC), a scientific resources platform.

The difficulty in obtaining a vaccine is given by the structure of the HIV envelope, which makes it very inaccessible to the action of neutralizing antibodies, details the virologist, who is not involved in the studies.

Given the difficulty of generating neutralizing antibodies against HIV, the authors of these new works guide the immune system to generate a specific type of neutralizing antibodies with different immunogens.

First simpler (so that they can be recognized better) and then more complicated and close to the original envelope protein of HIV, details Julià Blanco, head of the Virology and Cellular Immunology group at the IrsiCaixa AIDS Research Institute.

The HIV envelope protein has different regions that are recognized by neutralizing antibodies. For a specific region (the CD4 binding site), this strategy had already been used and has even reached human studies.

Now a second region appears (the base of the V3 loop) that can also be used in a similar way. “If both strategies are combined, a greater quantity and diversity of these neutralizing antibodies could be generated (which would make a potential vaccine more effective),” explains Blanco, who is not participating in the studies.

Sequential vaccination can be an excellent strategy, but it may require an excessive number of immunogens, which would make it difficult to convert it into a product that reaches the population most in need. “There is still a lot of work ahead,” summarizes SMC.

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