A Phase 1 study for a RSV vaccine candidate is also under way.
As part of its Vaccine Day this week, the company has updated its vaccine development timeline and unveiled results from early stage mRNA vaccine trials.
Moderna expects to begin three phase 1 clinical trials for two HIV vaccine candidates, mRNA-1644 and mRNA-1574, in 2021.
mRNA-1644 is a novel approach to HIV vaccine strategy in humans designed to elicit broadly neutralizing HIV-1 antibodies (bNAbs). It is being developed in collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation (BMGF). A Phase 1 study for the candidate will use iterative human testing to validate the approach and antigens and multiple novel antigens will be used for germline-targeting and immuno-focusing.
A second approach, mRNA-1574, is being evaluated with the US National Institutes of Health (NIH) and includes multiple native-like trimer antigens.
Moderna’s flu program is assessing multiple candidates, comprising multiple antigen combinations against the four seasonal viruses recommended by the WHO. The company expects to begin a Phase 1 clinical trial for the program this year.
Beyond this, it wants to explore potential combination vaccines against flu, SARS-CoV-2, RSV and human metapneumovirus (hMPV).
Current flu vaccines in the market have efficacy rates in the regoin of 40-60%: which Moderna believes its mRNA technology can improve on. It also says that its technology has several advantages over egg-based vaccine production: not only in terms of production advances but in accurately targetting vaccines against strains (egg-based production has the potential to cause unintended antigenic change to the vaccine virus).
Moderna has also released the interim analysis of its Phase 1 study for mRNA-1345, its RSV vaccine candidate, this week.
A single mRNA-1345 vaccination of 50 μg (N=19) or 100 μg (N=20) was generally well-tolerated in younger adults (ages 18-49 years).
The vaccine was shown to increase RSV neutralizing antibodies in seropositive younger adults. Neutralizing antibodies were also present at baseline in all participants, as expected. A single vaccination of mRNA-1345 at the 50 or 100 μg dose level boosted neutralizing antibody titers against both serotypes of RSV-A and RSV-B with no apparent dose response.
“I am encouraged by these interim Phase 1 data showing the ability of mRNA-1345 to elicit a strong neutralizing antibody response,” said Jacqueline Miller, M.D., Senior Vice President, Infectious Diseases, Moderna. “We will continue to pursue RSV vaccines to protect the most vulnerable populations – young children and older adults – where reducing RSV infection is also a significant unmet need. We will also be evaluating possible combinations of mRNA-1345 with other respiratory virus vaccines.”
There is currently no approved vaccine for Respiratory Syncytial Virus.
Moderna’s CMV vaccine is the most advanced of its mRNA vaccine candidates: and it will enter a Phase 3 pivotal study of 8,000 seronegative women aged 16-40 this year across the US, Europe and Asia-Pacific.
Moderna has released interim Phase 2 data for the vaccine, mRNA-1647, this week after seven months. In CMV-seronegative participants after 3 doses, neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were at least 20-fold higher than the baseline GMT of the CMV-seropositive group; while neutralizing antibody GMTs against fibroblast infection approximated the baseline GMT of the CMV-seropositive group.
In CMV positive participants, neutralizing antibody GMTs against epithelial cell infection increased to at least 6.8-fold over baseline, while neutralizing antibody GMTs against fibroblast infection increased to approximately 2-fold over baseline
mRNA-1647 is a vaccine combining six mRNAs in a single vial, which encode for two antigens located on the surface of CMV: five mRNAs encoding the subunits that form the membrane-bound pentamer complex and one mRNA encoding the full-length membrane-bound glycoprotein B (gB). Both the pentamer and gB are essential for CMV to infect barrier epithelial surfaces and gain access to the body. mRNA-1647 is designed to produce an immune response against both the pentamer and gB for the prevention of CMV infection.