According to scientists at the US National Institute of Allergy and Infectious Diseases (NIAID) – part of the National Institutes of Health, an experimental HIV vaccine is based on mRNA – the same technology used in the two highly effective COVID – 19 vaccine – shows promise in mice and primates.
Their results, published in the journal Nature Medicine, show that the new vaccine is safe and promotes cellular and antibody immune responses against the HIV virus. Rhesus monkeys, which received a primer vaccine followed by multiple booster vaccinations, were 79% less likely to be infected with simian-human immunodeficiency virus (SHIV) than unvaccinated animals. The study was led by Paolo Lusso, MD, associate professor, of NIAID's Immunomodulation Laboratory, in collaboration with other NIAID scientists, investigators from Moderna, Inc. and colleagues at other institutions.
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“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains elusive,” said NIAID Director Anthony S. Fauci, M.D., chief of the Laboratory and co-author of the paper. is an elusive goal. This experimental mRNA vaccine combines several features that may overcome the shortcomings of other experimental HIV vaccines and is therefore a promising approach."
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The experimental vaccine works similarly to the COVID-19 mRNA vaccine. However, instead of carrying mRNAs that code for the coronavirus spike protein, the vaccine provides coding for the two main proteins of HIV, Env and Gag. Animal muscle cells are injected with these two proteins to produce viral particles (VLPs) that attach multiple copies of Env to their surface. Although they cannot acquire infection and cause disease because they lack the complete genetic code of HIV, these VLPs are perfectly suitable in terms of stimulating immune responses for HIV.
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In studies with mice, two injections of a VLP-forming mRNA vaccine produced neutralizing antibodies in all animals. The Env proteins produced in mice from mRNAs closely resemble proteins in the whole virus, an improvement over previous experimental HIV vaccines. “Display of multiple copies of the authentic HIV envelope protein per VLP is one of the distinctive features of our platform, which closely mimics the natural infection process and may have played a role in stimulating the desired immune responses.”
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Then, the research team tested the mRNA Env – Gag VLP vaccine on monkeys. The details of vaccine regimens vary between animal subgroups but involve supplementing the immune system with vaccines modified to optimize antibodies. This is followed by multiple booster vaccinations over the course of a year. The booster vaccine contains Gag mRNA and Env mRNA from two HIV groups different from the group receiving the main vaccine. Investigators used multiple viral variants to preferentially activate antibodies against more conserved "shared regions" of Env - the target of neutralizing antibodies - rather than variable regions different for each virus strain.
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Despite the high dose of mRNA delivered, the vaccine was well tolerated and produced only mild, temporary side effects in the monkeys such as loss of appetite. By week 58, all vaccinated zebra monkeys had developed measurable levels of neutralizing antibodies against most strains in a panel of 12 diverse HIV strains. In addition to inducing neutralizing antibodies, VLP mRNA vaccines also induce a strong response of helper T cells.
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Beginning at week 60, vaccinated and control animals were exposed weekly, via rectal mucosa, to SHIV. Because nonhuman primates are not susceptible to HIV-1 infection, scientists use SHIV in laboratory settings because that virus replicates in monkeys. After 13 weekly infectious injections, two of seven vaccinated monkeys remained uninfected. Other vaccinated animals experienced a slower onset of infection, occurring on average after 8 weeks. In contrast, unvaccinated animals become infected on average after 3 weeks.
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“We are currently refining our vaccination process to improve the quality and quantity of VLPs produced. This may further increase vaccine effectiveness and thereby reduce the number of prime and booster vaccinations needed to induce a strong immune response. If confirmed to be safe and effective, we plan to conduct phase 1 testing of this vaccine platform in healthy adult volunteers.” Dr. Lusso said.
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Translator: Thanh Long – Phacogen Institute of Technology,
Bachelor of Biotechnology - University of Natural Sciences - Hanoi National University
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Source of article: https://www.sciencedaily.com/releases/2021/12/211209124236.htm
(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)
