Experimental HIV mRNA vaccine shows promise

Experimental HIV mRNA vaccine shows promise

An experimental mRNA-based HIV vaccine, the same platform technology used in two highly effective COVID-19 vaccines. It shows promise in mice and nonhuman primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID).

Results show the new vaccine was safe

Their results, published in Nature Medicine, show that the new vaccine was safe. And it elicited the desired cellular and antibody immune responses against an HIV-like virus.

Rhesus macaques that received a booster vaccine followed by multiple booster shots had a 79% lower risk of infection. This, by the simian human immunodeficiency virus (SHIV) per challenge compared to unvaccinated animals.

The research was led by Paolo Lusso, MD, Ph.D., of the NIAID Immunoregulation Laboratory, in collaboration with other NIAID scientists, Moderna, Inc. researchers, and colleagues at other institutions.

Despite nearly four decades of effort by the global research community. An effective vaccine to prevent HIV remains an elusive goal. ” Said NIAID Director Anthony S. Fauci, MD, head of the lab and a co-author of the paper. “This experimental mRNA vaccine combines several characteristics that can overcome the shortcomings of other experimental HIV vaccines. And therefore it represents a promising approach ”.

Experimental vaccine works like COVID-19 mRNA vaccines

The experimental vaccine works like the COVID-19 mRNA vaccines. However, instead of carrying mRNA instructions for the coronavirus spike protein. The vaccine delivers coded instructions for making two key HIV proteins, Env and Gag.

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The muscle cells of an inoculated animal assemble these two proteins to produce virus-like particles (VLPs). Studded with numerous copies of Env on their surface. Although they cannot cause infection or disease because they lack the complete genetic code of HIV. These VLPs match complete infectious HIV in terms of stimulating adequate immune responses.

In mouse studies, two injections of the VLP-forming mRNA vaccine induced neutralizing antibodies in all animals. Investigators report.

The Env proteins produced in the mice from the mRNA instructions closely resembled those of the whole virus. An improvement over previous experimental HIV vaccines. “The visualization of multiple copies of the authentic HIV envelope protein in each VLP. It is one of the special features of our platform that closely mimics natural infection and may have played a role in eliciting the desired immune responses. ” Dr. Lusso said.

The team tested the Env-Gag VLP mRNA vaccine in macaques

The team then tested the Env-Gag VLP mRNA vaccine in macaques. The details of the vaccine regimen differed between the subgroups of vaccinated animals. But they did involve priming the immune system with a modified vaccine to optimize antibody creation.

The cousin was followed by multiple booster shots administered over the course of a year. The booster vaccines contained Gag mRNA and Env mRNA from two different clades of HIV from the one used in the main vaccine. The researchers used multiple virus variants to preferentially activate antibodies against the more conserved “shared” regions. Instead of the most variable regions that differ in each virus strain.

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.

By week 58, all vaccinated macaques had developed measurable levels of neutralizing antibodies directed against most strains in a test panel of 12 different HIV strains. In addition to neutralizing the antibodies, the VLP mRNA vaccine also induced a robust T helper cell response.

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