More than four decades have elapsed since the onset of the HIV/AIDS pandemic and a protective vaccine has yet to be developed. There are different hurdles responsible for this lack of success, including the antigenic variability of the HIV-1 envelope (env), the protected configuration of the virus and the in vivo rarity of B cells expressing germline precursors of broadly neutralizing antibodies.
Different vaccine approaches have been evaluated in preclinical models and clinical studies, but the results have been unsatisfactory.
New Experimental Vaccine
An experimental HIV vaccine based on the mRNA technology, the same one used in the two highly effective COVID-19 vaccines shows promise in mice and non-human primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID).
The results of their study were published in the journal Nature Medicine, and showed that the novel vaccine was safe and prompted desired antibody and cellular immune responses against an HIV-like virus. They used rhesus macaques and inoculated them with a priming vaccine followed by multiple boosters, having a 79% lower per-exposure risk of infection by simian human immunodeficiency virus (SHIV) compared to unvaccinated animals.
“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. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”
The experimental vaccine works like mRNA COVID-19 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. Muscle cells in 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 whole, infectious HIV in terms of stimulating suitable immune responses.
Although the doses of mRNA delivered were high, the vaccine was well tolerated and produced only mild, 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 diverse HIV strains. In addition to neutralizing antibodies, the VLP mRNA vaccine also induced a robust helper T-cell response.
Beginning at week 60, immunized animals and a control group of unimmunized macaques were exposed weekly, via the rectal mucosa, to SHIV. Because non-human primates are not susceptible to HIV-1, scientists use a chimeric SHIV in experimental settings because that virus replicates in macaques. After 13 weekly inoculations, two out of seven immunized macaques remained uninfected. The other immunized animals had an overall delay in infection, which occurred, on average, after eight weeks. In contrast, unimmunized animals became infected on average after three weeks.
Peng Zhang, et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques. Nature Medicine, 2021; DOI: 10.1038/s41591-021-01574-5
NIH/National Institute of Allergy and Infectious Diseases. “Experimental mRNA HIV vaccine safe, shows promise in animals.” ScienceDaily. ScienceDaily, 9 December 2021. <www.sciencedaily.com/releases/2021/12/211209124236.htm>.