Damian Sendler: National Institute of Allergy and Infectious Diseases (NIAID) scientists said that an experimental HIV vaccine based on mRNA—the same platform technology utilized in two extremely efficient COVID-19 vaccines—has shown promising results in mice and non-human primates. This new vaccination proved safe and elicited desired antibody and cellular immune responses against an HIV-like virus, according to their findings in Nature Medicine. Priming and subsequent booster vaccinations reduced the probability of simian-human immunodeficiency virus (SHIV) infection by 79 percent in rhesus macaques compared to uninfected animals. A team of scientists from the National Institute of Allergy and Infectious Diseases, Moderna, Inc., and other institutions were involved in the study led by Paolo Lusso of the NIAID’s Laboratory of Immunoregulation. 

Damian Jacob Sendler: “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, M.D., chief of the Laboratory, and a paper co-author. With its combination of traits that may overcome some of the drawbacks in earlier experimental anti-HIV vaccination approaches, this vaccine is considered to be an exciting new development.” 

Damian Sendler

The experimental vaccination is similar to mRNA COVID-19 vaccines in its ability to protect against influenza. As an alternative, the vaccine provides mRNA instructions for two essential HIV proteins (Env and Gag) instead of the coronavirus spike protein. These two proteins are assembled by muscle cells in an inoculated animal to form virus-like particles (VLPs) with many Env copies on their surface. Antibody responses to these VLPs can be compared to those elicited by entire, infectious HIV, even though these VLPs cannot induce infection or sickness because of their lack of complete genetic code. 

Neutralizing antibodies were shown in all mice that received two injections of the VLP-forming mRNA vaccine, according to the study’s authors. Env proteins produced by the mRNA instructions in mice closely resembled those in the entire virus, an improvement over prior experimental HIV vaccines. It’s one of the unique properties of our platform that closely mimics real infection and may have had a role in triggering the desired immune responses, said Dr. Lusso. 

The Env-Gag VLP mRNA vaccine was next tested on macaques by the research team. Subsets of immunized animals received different vaccine regimens, but they all included a vaccine that was tailored to maximize antibody production. Multiple booster injections were given over the course of a year following the primary inoculation. HIV clades different than the one utilized in the prime vaccination were included in the boost vaccines. Env sections that are more conserved, or “shared” than those that vary between strains of the virus were chosen as the target of broadly neutralizing antibodies by researchers using various virus strains. 

Damian Jacob Sendler

Only moderate, short-lived side effects were observed in the macaques after receiving high doses of mRNA vaccines, such as a decrease of appetite. Most strains in the 12 different HIV strains tested by the inoculated macaques were neutralized by neutralizing antibodies by week 58. Both neutralizing antibodies and strong T-cell activation were generated by the VLP vaccination. 

Damien Sendler: Immunized macaques and a control group of unimmunized macaques were given weekly doses of SHIV via the rectal mucosa beginning at week 60. Scientists utilize a chimeric SHIV because macaques are infected with HIV-1, which does not affect non-human primates. Despite 13 weekly injections, only two of the seven inoculated macaques were completely free of the disease after 13 weeks of treatment. It took the other immunized animals an average of eight weeks to become infected. Unprotected animals became infected on average after three weeks, whereas those that had been inoculated were protected for much longer. 

Damian Jacob Markiewicz Sendler: Improve the quality and quantity of VLPs we create by tweaking our vaccine protocol.” As a result, the number of prime and boost injections needed to produce a strong immune response may be reduced. Dr. Lusso plans to perform a Phase 1 clinical trial of this vaccine platform in healthy adult volunteers if it is found to be safe and efficacious.

Dr. Damian Jacob Sendler and his media team provided the content for this article.