mRNA Technology Leads to Advances in HIV Vaccine Candidate

Messenger RNA (mRNA) vaccines have made a remarkable impact on
the trajectory of the COVID-19 pandemic. The success of these vaccines raises the question of whether this technology can be used to tackle the more complex task of creating a vaccine to fight HIV.

Nearly 37.7 million people were living with HIV in 2020 and 680,000 people died because of related illnesses, according to statistics provided by the United Nations Programme on HIV/ AIDS.¹ In 2020, during the height of the COVID-19 pandemic, the Global Fund to Fight AIDS, Tuberculosis, and Malaria reported a 41% decrease in HIV testing and a 37% decrease in
the diagnosis and treatment of HIV/AIDS across 32 countries in Africa and Asia.² It is clear more effort is needed to make an impact on the ever-growing HIV epidemic.

mRNA vaccines may be 1 piece of this expanded effort. They are, accord- ing to Nature Medicine,³ a “uniquely positioned” technology. At Moderna,
2 mRNA HIV vaccines are being developed. The first, mRNA-1644, is being created in conjunction with the International AIDS Vaccine Initiative and the Bill and Melinda Gates Foundation. The second, mRNA-1574, is being evaluated in collaboration with the National Institutes of Health. In late January, Moderna announced the first patient in the mRNA-1644 phase 1 clinical trial (NCT05001373) was dosed.⁴

A recent study, also published in Nature Medicine,⁵ led by Paolo Lusso, MD, PhD, of the National Institute of Allergy and Infectious Diseases, sought to determine whether mRNA-expressing membrane-anchored HIV-1 enve- lopes (Env) and simian immunodeficiency virus Gag proteins can generate viruslike particles that induce antibodies that neutralize and reduce infec- tion in monkeys and mice. This preclinical study evaluated a multiclade HIV-1 env-gag mRNA vaccine in animal models, where the vaccine’s efficacy was evaluated based on time to infection over a 13-week period of low-dose vaccine administration.

This same technology used to create the COVID-19 vaccines showed positive results in monkeys and mice. Instead of targeting the SARS- CoV-2 spike protein, the vaccine targets 2 essential HIV proteins, Env and Gag. The study results showed vaccinated animals had a 79% risk reduction per vaccine exposure. In the studied mice, Lusso and colleagues reported the Env proteins greatly resembled those in the entire virus. Among the monkeys, 2 of the 7 subjects remained unaffected after the 13-week inoculation schedule, suggesting the virus-particle mRNA platform is a capable approach for the development of an HIV vaccine.

Although the results suggested benefits, the authors acknowledged some study limitations. First, the neutralization titers to combat the virus did not reach optimal levels that have been reported by other studies as protective in the body. Only 2 animals were fully protected by the vaccine. However, the particular strain investigators were trying to neutralize was challenging, and the vaccine still induced a 79% risk reduction per exposure. Finally, this vaccine has been tested in only 1 study, and more studies should be done to confirm these findings.

mRNA technology may be the right platform to develop vaccines
for different disease states, but more studies must be done. The study by Zhang et al provided more information on the positives this technology presents. It proved this vaccine is safe, immunogenic, and can induce CD4 T-cell responses in animals—and potentially in humans.

Kmeone Kingdom, MPH, is currently a PharmD candidate at the South College School of Pharmacy, anticipated to graduate in spring 2022. This article was created during a virtual advanced pharmacy practice experiential rotation at STACK.

References

1. Global HIV & AIDS statistics — fact sheet. United Nations Programme on HIV/AIDS. Accessed February 7, 2022. https://www.unaids.org/en/resources/fact-sheet
2. New Global Fund report shows massive disruption to health care caused by COVID-19 in Africa and Asia. The Global Fund. April 13, 2021. Accessed February 7, 2022. https://www.theglobalfund.org/en/news/2021-04-13-new-global-fund-report-shows-massive-disruption-to-health-care-caused-by-covid-19-in-africa-and-asia/
3. IAVI and Moderna launch trial of HIV vaccine antigens delivered through mRNA technology. News release. Moderna, Inc; January 27, 2022. Accessed February 7, 2022. https://investors.modernatx.com/news/news-details/2022/IAVI-and-Moderna-Launch-Trial-of-HIV-Vaccine-Antigens-Delivered-Through-mRNA-Technology/default.aspx
4. Morris L. mRNA vaccines offer hope for HIV. Nat Med. 2021;27(12):2082-2084. doi:10.1038/s41591-021-01602-4
5. Zhang P, Narayanan E, Liu Q, 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. Nat Med. 2021;27(12):2234-2245. doi:10.1038/s41591-021-01574-5