Mon. Jan 24th, 2022

Scientists have developed an experimental HIV vaccine that uses messenger RNA (mRNA) the same platform technology used in two highly effective COVID-19 vaccines to deliver antigens to cells of the immune system, where they trigger the production of antibodies against HIV. Human trials of an experimental vaccine based on mRNA (messenger RNA) have shown promising results in laboratory testing in animals on mice and non-human primates, according to the study published by on NIH/National Institute of Allergy and Infectious Disease. If found safe and effective in people, the vaccine could help prevent the spread of HIV, the virus that causes AIDS. Since it was first identified nearly 35 years ago, scientists have struggled to create an effective preventive HIV vaccine that would induce immune responses similar to natural infection with the virus.

Popular New Approach

The experimental vaccine functions similarly to COVID-19 mRNA vaccines. Instead of mRNA instructions for the coronavirus spike protein, the vaccine contains coded instructions for the production of two important HIV proteins, Env and Gag. Muscle cells of an infected animal combine these two proteins to form virus-like particles (VLPs) with multiple copies of Env on their surface. The vacancies use fragments of genetic material called messenger RNA (mRNA). These fragments carry instructions from genes to cells. They are now studying whether delivering these fragments by injection could stimulate immune cells to ward off infection by HIV. Scientists delivered synthetic mRNA vaccines into the muscle tissue of several non-human primates, including mice, The vaccines worked safely and effectively: following vaccination, immune cells produced antibodies against HIV proteins—the first step toward warding off infection.

The researchers claim that two injections of the VLP-forming mRNA vaccine produced neutralizing antibodies in all mice in their trials. The Env proteins made in mice from mRNA instructions were quite similar to those found in the whole virus, which was an improvement above earlier HIV vaccines. “One of the unique features of our platform that closely replicates natural infection is the presence of numerous copies of actual HIV envelope protein on each VLP,” said Dr. Lusso (M.D – NIH/National Institute of Allergy and Infectious Diseases). “This may have played a role in eliciting the optimal immune responses.”

The Env-Gag VLP mRNA vaccine was then tested in macaques. The vaccine regimen varied depending on the subgroups of vaccinated animals, but it always entailed priming the immune system with a vaccine that had been tweaked to maximise antibody production. Multiple booster inoculations were given over the period of a year after the initial shot. Gag mRNA and Env mRNA from two HIV clades other than the one utilized in the prime vaccination were included in the boost vaccines. The researchers utilised a variety of virus strains to activate antibodies against the more conserved “shared” sections of the Env, which are the target of broadly neutralising antibodies, rather than the more variable areas that differ from virus to virus.

Despite the enormous amounts of mRNA supplied, the vaccine was well tolerated by the macaques, who experienced only minor, transient side effects such as loss of appetite. In a test panel of 12 different HIV strains, all vaccinated macaques had produced significant levels of neutralising antibodies directed against the majority of them by week 58. The VLP mRNA vaccination elicited a strong helper T-cell response in addition to neutralising antibodies.

Immunized animals and a control group of unimmunized macaques were exposed to SHIV weekly via the rectal mucosa beginning at week 60. Because nonhuman primates are immune to HIV-1, scientists utilise a chimeric SHIV virus in experiments because it replicates in macaques. Two out of seven inoculated macaques remained uninfected after 13 weekly inoculations. The other immunized animals experienced a delay in infection, which took an average of eight weeks to occur. Unimmunized animals, on the other hand, become infected after three weeks on average.

“Our vaccine technique is now being refined in order to improve the quality and quantity of VLPs produced. This could raise vaccine efficacy, even more, reducing the number of primes and boosting vaccinations required to generate a strong immune response. We intend to conduct a Phase 1 study of this vaccine platform in healthy adult volunteers if it is found to be safe and efficacious “Dr. Lusso stated.

Challenges Remain

An experimental HIV vaccine tested in Mice is both safe and effective in eliciting an immune response against a common form of AIDS. The next step is to test it further in humans. Despite decades of work on vaccines against HIV, there’s still no broadly-effective one that protects people from getting infected with—and being vulnerable to—the virus that causes AIDS. That’s likely because existing vaccine efforts have focused on mimicking proteins found on the surface of HIV itself.

Source: NIH/National Institute of Allergy and Infectious Diseases

By Anshul

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