Trial of Three mRNA HIV Vaccines Launched
Trial of Three mRNA HIV Vaccines Launched
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A Phase I clinical trial will explore the safety and immunogenicity of three preventive HIV vaccines using mRNA technology.
HVTN 302 clinical trial
The study – named HVTN 302 – will test three experimental vaccines: BG505 MD39.3 mRNA, BG505 MD39.3 gp151 mRNA and BG505 MD39.3 gp151 CD4KO mRNA in ~108 healthy participants aged 18–55 years. These experimental vaccines are manufactured by the biotech company Moderna in contract with the National Institute of Allergy and Infectious Diseases (NIAID).
How do mRNA vaccines work?
Messenger ribonucleic acid (mRNA) encoding a particular viral protein induces endogenous production of the protein in the recipient's cells. This prompts an immune response ensuring that the body “remembers” the virus.
Instead of encoding the SARS-CoV-2 spike protein, as is the case for the COVID-19 mRNA vaccines, the three vaccines in HVTN 302 encode trimers – stabilized proteins found on the surface of HIV. These proteins are essential for HIV to enter human cells and cause infection. Each of the three mRNA sequences, developed through the work of Steichen et al, encode a slightly different form of the protein.
HVTN 302 trial structure
The trial’s principal investigators are Dr. Jesse Clark, associate professor-in-residence in the department of medicine at the University of California Los Angeles, and Dr. Sharon Riddler, associate chief of clinical research at the University of Pittsburgh. Eleven sites across the US will be recruiting participants for the trial, who will be randomly allocated to receive three doses of one of the mRNA vaccines. The trial, which is expected to be complete by July 2023, is structured as follows:
Group A – Three groups of 18 participants will receive intramuscular injection (100 mcg) of assigned vaccine at baseline, month two and month six.
- Subject to initial safety criteria evaluation, Group B will then be dosed.
Group B – Three groups of 18 participants will receive intramuscular injection (250 mcg) of assigned vaccine at baseline, month two and month six.
“The primary hypothesis is that the BG505 MD39.3 soluble and membrane-bound trimer mRNA vaccines will be safe and well-tolerated among HIV-uninfected individuals and will elicit autologous neutralizing antibodies,” ClinicalTrials.gov reads.
Difficulties in developing a HIV vaccine
Despite several decades of research, a preventive – or therapeutic – vaccine for HIV does not yet exist. Note that this is not for lack of trying; HIV is an incredibly complex virus that is very good at mutating. In the pre-clinical development of a drug or preventive vaccine, animal trials are necessary to determine the safety and effectiveness of the investigational medicinal product (IMP). A virus that mutates often and rapidly is difficult to model, therefore making this key step in the IMP development particularly challenging. If we can’t test in animals, we cannot progress to testing in humans.
In addition – while there are some exceptions – humans infected with HIV do not become immune to the virus. The typical approach for immunization is to mimic a natural immune response. Of course, if one doesn’t exist, this can’t be achieved.
Is mRNA technology a solution?
The first mRNA vaccine authorized for emergency use in humans came in 2020. However, decades of research preceded this pivotal moment for the mRNA field and the pandemic response.
“Finding an HIV vaccine has proven to be a daunting scientific challenge,” said Anthony S. Fauci, M.D. NIAID director. “With the success of safe and highly effective COVID-19 vaccines, we have an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”
mRNA technology has been poised as a potential solution to some of the issues associated with HIV vaccine development. “mRNA vaccines allow the rapid development of vaccines using different genetic sequences, and thus different antigens,” Dr. Peter English, retired consultant in communicable disease control and member of the editorial board for Vaccines Today, previously told Technology Networks. “This could mean developing vaccines that produce a range of different antigens, to cope with the diversity of the HIV virus […] it could allow studies to try out a wider range of antigens to study their efficacy in initial laboratory studies."
HVTN 302’s launch is hot on the heels of Moderna’s announcement that it dosed its first patient with a mRNA HIV vaccine – mRNA-1574 – on Monday. The Phase I trial will test the vaccine’s safety and immunogenicity in 100 HIV-negative individuals aged <55 years.
In January, the non-profit organization International AIDS Vaccine Initiative (IAVI) – again in partnership with Moderna – launched a Phase I trial, IAVI G002. Taking a slightly different approach, this trial is exploring whether sequential administration of HIV immunogens delivered using mRNA technology can induce B-cell responses, directing their maturation towards broadly neutralizing antibody (bnAb) development.
There are no certainties as to whether mRNA technology will be the long sought-after answer to HIV vaccine development challenges, but it’s clear that both academia and industry are invested in finding out.