A messenger RNA vaccine against HIV shows promise in animals

An experimental vaccine against HIV shows promise in mice and non-human primates. The data indicate that it is safe and elicits the desired cellular and antibody immune responses against a human immunodeficiency-like virus.

The study published this Thursday by Nature Medicine has been developed by the National Institute of Allergies and Infectious Diseases (NIAID), which is part of the National Institutes of Health of the United States.

The experimental vaccine is based on messenger RNA (mRNA), the same technology used for some vaccines against COVID-19, and rhesus macaques inoculated with the preparation and multiple booster doses had a 79% lower risk of infection by the virus. simian immunodeficiency (VISH).

Non-human primates are not susceptible to HIV-1 (the most common type in the world) and scientists use a chimeric VISH in experimental settings because it replicates in macaques.

"Despite nearly four decades of efforts by the global research community, an effective vaccine to prevent HIV remains an elusive goal," said NIAID Director Anthony S. Fauci, a co-author of the paper.

This preparation combines "several characteristics that can overcome the deficiencies of other experimental vaccines against HIV and, therefore, represents a promising approach," Fauci said in a statement.

The experimental vaccine works like the mRNA-based COVID-19 vaccine, but instead of carrying instructions for the coronavirus spike (S) protein, it has coded instructions for making two key HIV proteins, Env and Gag.

Muscle cells from an inoculated animal assemble these two proteins to produce virus-like particles (VLPs) with numerous copies of Env on their surface.

Although they cannot cause infection or disease because they lack the complete genetic code, these VLPs match infectious HIV in terms of stimulating adequate immune responses.

In mouse studies, they induced neutralizing antibodies in all animals, and the Env proteins produced closely resembled those of the whole virus, an improvement over previous experimental HIV vaccines.

The team also tested the preparation in macaques, and the first inoculation was followed for a year by multiple booster doses containing Gag and Env messenger RNA from two different HIV clades than the main one.

Although the doses of mRNA administered were high, "the vaccine was well tolerated and produced only mild and temporary adverse effects in the macaques, such as loss of appetite," the note adds.

By week 58, the vaccinated macaques had developed measurable levels of neutralizing antibodies directed against most strains out of a set of 12 and further induced a robust T helper cell response.

Starting at week 60, immunized animals and a control group of unimmunized macaques were challenged weekly to VISH.

After thirteen weekly inoculations, two of the seven immunized macaques were still not infected and the other animals that had been vaccinated showed "a general delay in infection, which occurred, on average, after eight weeks".

The non-immunized, however, were infected, on average, after three weeks.

The team is now refining the vaccination protocol to improve the quality and quantity of the VLPs produced, which can further increase the efficacy of the vaccine and therefore reduce the number of primary and booster inoculations required to generate a robust immune response, noted the report's lead researcher Paolo Lusso.


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