Moderna revealed the first interim results from a small, Phase I study of its mRNA-based influenza vaccine, which showed that the vaccine had no significant safety concerns and elicited immune responses against four strains of the influenza virus.
After the success of its first and very timely commercial product Spikevax — Moderna’s mRNA vaccine for COVID-19 — Moderna leveraged the same mRNA technology to create a vaccine against influenza.
And it did so in a speedy manner similar to that of its COVID-19 shot. Moderna designed its mRNA influenza vaccine in January of this year and began human testing just five months ago, highlighting the speed at which mRNA vaccines can be developed.
The quadrivalent influenza vaccine candidate, mRNA-1010, is targeted against hemagglutinin (HA) proteins from four seasonal influenza viruses, which include two influenza A subtypes, H1N1 and H3N2, and two influenza B subtypes, Yamagata and Victoria. These strains of the virus were recommended by the World Health Organization (WHO).
The vaccine successfully boosted HA antibody titers against all strains 29 days after vaccination with all of the doses evaluated in both young and older adults. Antibody levels against the A strains were higher than the B subtypes. Moderna said the mixed results warrant further investigation, which the company will pursue in its planned Phase II trial for mRNA-1010.
The company also announced that it has two other quadrivalent flu vaccine candidates, mRNA-1011 and mRNA-1012, in the pipeline as part of its seasonal flu vaccine program.
Given that annual influenza vaccines have an efficacy of 40 percent to 60 percent, there is scope for improvement. The lower effectiveness is partly due to the significant lead time involved in designing and manufacturing the vaccines, which can lead to mispredictions of which influenza strains will dominate during a given season. Moderna believes the speed and flexibility of its mRNA platform will allow for the design of vaccines closer to flu season when there is a better picture of which strains should be targeted that year.
Moderna’s ultimate goal is to have a single shot booster vaccine that protects against a trifecta of respiratory infections including COVID-19, influenza and respiratory syncytial virus (RSV).
First Trial Results for First mRNA Influenza Vaccine
In the Phase I study evaluating mRNA-1010, doses of 50 µg, 100 µg and 200 µg were tested in groups of younger adults (age 18 to 49) and older adults (50 years of age and older); each group had 45 participants. After a period of 29 days post-vaccination, antibody levels against H1N1 and H3N2 increased ten-fold and eight-fold, respectively in adults aged 18 to 49, and by 6-fold for each in adults over 50. Immunogenicity against the two influenza B strains was lower, with three-fold and two-fold antibody increases for Yamagata and Victora, respectively, in both age groups.
There were no significant safety findings reported through day 29. Adverse reactions were observed at higher doses and generally occurred more frequently in younger adults compared to older adults. Higher doses did not yield stronger immune responses, which led Moderna to settle on the 50 µg for its planned Phase II trial. However, it is also going to test the 25 µg dose as well, leading to speculation of potential safety concerns. The most common local adverse reactions for both age groups included pain and axillary swelling/tenderness, while common systemic reactions for both age groups included fatigue, arthralgia (joint stiffness), myalgia and headache.
“The positive interim results from our Phase I quadrivalent flu vaccine candidate, mRNA-1010, are an important milestone toward achieving that goal. It is encouraging to see that participants in the study who received the 50 µg dose, including older adults, achieved robust increases in geometric mean antibody titers against H1N1 and H3N2, the strains responsible for the vast majority of morbidity and mortality in this age group,” Moderna President Stéphane Bancel said in a company statement.
“We believe our mRNA platform is well-positioned to address the significant unmet need in seasonal flu as evidenced by our new beyond quadrivalent candidates, mRNA-1011 and mRNA-1012, which we believe will expand strain coverage and provide more options for public health officials,” Stéphane Bancel continued.
However, considering the more robust immune responses observed against the influenza A subtypes over the B subtypes, Bancel said in a conference call that, “it is a bit of a mixed picture and strain specific” at this point. As such, he cautioned that, “We have to be careful about over interpreting” the data, given the small number of patients in the study.
While the initial results are promising, it remains to be seen how Moderna’s mRNA-based vaccine will stack up against the current vaccines. In a separate study, data from which Moderna also shared, Moderna’s influenza vaccine appeared to be similar to a high dose of Sanofi’s Fluzone vaccine. Moderna said the results were preliminary and that the Phase II study is needed for more robust data.
Current influenza vaccines are also typically quadrivalent, and contain inactivated or live attenuated forms of the full viruses.
Moderna also announced that enrolment for the Phase II study of mRNA-1010 is now complete and that plans for the Phase III study are currently underway.
Moderna isn’t the only one with mRNA-based influenza vaccines in development. Pfizer, GlaxoSmithKline and Sanofi are also looking to develop mRNA flu shots with their partners BioNTech, CureVac and Translate Bio, respectively. Sanofi acquired the latter earlier this year.