HIV-preventing mRNA vaccine gives good results in animals

An experimental HIV vaccine based on mRNA, the technology behind two highly effective Covid-19 vaccines, has shown positive results in mice and primates.

Research results published in the journal Nature Medicine on December 9 by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) show that the new vaccine is safe, produces antibodies and immune responses in cells. cells against HIV-like viruses. Golden monkeys given the primary vaccine dose, followed by multiple booster shots, had a 79% lower risk of exposure to monkey immunodeficiency virus (SHIV) compared with unvaccinated animals. The study was conducted by Dr. Paolo Lusso at the NIAID Immunosurveillance Laboratory, along with many scientists from the same institute and Moderna.

Scanning electron microscopy image of HIV-infected H9 T cells.

"Despite the efforts of the global research community for nearly four decades, an effective HIV vaccine remains a distant goal," said Anthony S. Fauci, director of NIAID and co-author of the study. . "This experimental mRNA vaccine combines several features that could overcome many of the limitations of other experimental HIV vaccines, so it is a promising approach."

The new vaccine works like the Covid-19 mRNA vaccine. However, instead of carrying the mRNA information for the nCoV spike protein, the vaccine provides the coding information to produce two key HIV proteins, Env and Gag. Muscle cells in immunized animals assemble these two proteins to produce a virus seed (VLP) with multiple copies of Env on its surface. Although not infectious due to the lack of HIV's complete genetic code, these VLPs are similar to HIV in terms of stimulating the appropriate immune response.

In a study with mice, two doses of the mRNA vaccine produced antibodies that neutralized the virus in all animals. The Env protein produced in mice from the mRNA information is very close to the complete viral protein. This is a big improvement over previous HIV vaccines tested. According to Dr. Lusso, the presence of multiple copies of the real HIV envelope protein in each VLP is one of the unique features that closely mimic the natural infection mechanism, which can contribute to the immune response. desire.

The team continued to test the Env-Gag VLP mRNA vaccine in golden monkeys. The dose of the vaccine varied between groups of monkeys, but all included a basic dose and multiple booster shots over a one-year period. The booster vaccine contains Gag mRNA and Env mRNA from two groups of HIV viruses instead of one as in the primary injection. The team used multiple viral strains to activate antibodies.

Although the dose of the mRNA vaccine was quite high, the product produced only very mild temporary side effects in golden monkeys such as loss of taste. By week 58, all vaccinated monkeys had developed neutralizing antibody levels targeting the most common of the 12 HIV strains used in the trial. In addition to antibodies, the VLP mRNA vaccine also produces an intense T-cell response.

Beginning at week 60, animals were immunized and a group of unvaccinated golden monkeys were exposed weekly to SHIV through rectal mucus. Since primates are unaffected by the HIV-1 strain, the scientists used a hybrid SHIV in their experiments because the virus replicates in golden monkeys. After 13 weeks of vaccination, 2 out of 7 immunized monkeys were unaffected by the virus. The remaining animals were infected more slowly (average of 8 weeks). In contrast, unvaccinated animals became infected after 3 weeks on average.

"We are improving the vaccine to improve the quality and quantity of the VLP. This could increase the effectiveness of the vaccine, thereby reducing the number of shots needed to generate a strong immune response. If confirmed. Safe and effective, we plan to test phase 1 of the vaccine in healthy adult volunteers," said Dr. Lusson.