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Flu vaccines and oncology are two potential areas that could fuel mRNA in the future. CureVac, in collaboration with GSK, recently announced promising phase 2 interim data from their seasonal influenza vaccine development program. The multivalent vaccine candidate, which encodes antigens matched to all four WHO-recommended flu strains, boosted antibody titers at all dose levels and across all age groups. The candidate showed strong performance against influenza A strains, with geometric mean titers numerically beating those elicited by licensed comparator vaccines. While the vaccine’s response against influenza B strains was lower than comparators, CureVac intends to optimize the vaccine to enhance immune responses against these strains in an additional phase 2 study.
Moderna and Pfizer are further along. The former is advancing its mRNA flu vaccine candidate mRNA-1010, which is being studied against high dose Fluzone HD in a fully enrolled phase 3 study. The company intends to file for regulatory approval in 2024. It is also developing a vaccine candidate, mRNA-1083, against flu and COVID-19. It is targeting regulatory approval for the combination vaccine in 2025.
In October 2023, Pfizer announced that its mRNA flu vaccine candidate met both primary endpoints in a phase 3 trial involving participants aged 18 to 64 years old. Yet the vaccine demonstrated non-inferiority and superiority to a licensed flu vaccine. Yet the vaccine missed a secondary endpoint related to immunogenicity for influenza B strains.
One possibility is that mRNA-based flu vaccines will tend to generate more side effects than traditional flu vaccines. In a phase 3 study, for instance, Moderna’s experimental mRNA flu vaccine generated a stronger immune response than a currently marketed traditional vaccine, but the safety findings were similar to previous mRNA vaccine studies, with muscle pain, headache, fatigue, pain and swelling topping the list of the most common reactions.
An analysis of patient-reported outcomes during the last flu season found that simultaneous administration of a COVID-19 mRNA booster and a flu vaccine resulted in a roughly 10% increased risk of mild systemic reactions compared to receiving the COVID-19 booster alone.
Sanofi has acknowledged the promise and perils of mRNA flu vaccines
Sanofi, a prominent flu vaccine maker, has acknowledged both the challenges and the potential of mRNA technology for flu. In a presentation earlier in 2023, the company shared market research noting that health care professionals will likely be reluctant to adopt mRNA-based flu vaccines with storage requirements more stringent than standard refrigeration. Additional market research notes that just under 70% of health care providers and patients would be unlikely to use mRNA vaccines with triple the severe side effect burden compared to a standard dose of traditional flu vaccine. A 2022 study of more than 35,000 adults from nine countries found that the novelty of mRNA vaccine technology increased hesitancy compared to conventional vaccines. Since then, demand for mRNA-based COVID vaccines has continued to steeply drop.
Graphic showing health care providers (HCPs) and consumers’ reluctance toward vaccines with three times as many severe side effects compared to the standard of care flu vaccine. Source: Sanofi Company Presentation.
Despite challenges, Sanofi still lists an mRNA vaccine candidate on its pipeline page. Sanofi announced positive interim data from an early phase 1/2 study of its mRNA flu vaccine in September 2021. The SP0273 vaccine demonstrated favorable reactogenicity compared to other mRNA candidates in adults aged 18-64. Sanofi’s SP0273 vaccine also showed favorable reactogenicity compared to other mRNA candidates in the same age group (18 to 64 years old).
In addition to mRNA-based vaccine designs, Novavax was developing a next-generation flu vaccine, qNIV (NanoFlu), using a different approach. The company’s quadrivalent nanoparticle vaccine, which targets seasonal flu using recombinant technology, successfully completed two phase 3 studies. The company, however, now only cites three products on its website — its authorized COVID-19 vaccine, a joint COVID/flu vaccine in phase 2 and a preclinical malaria vaccine.
The cost question
Traditional flu vaccines tend to be inexpensive — generally in the low tens of dollars per dose. As STAT News has pointed out, pundits believe it is unlikely that mRNA-based flu vaccines would cost less than traditional flu vaccines. Given that likelihood, mRNA flu shot makers will need to show their vaccines are substantially more effective than current options. To win a preferential recommendation from the CDC’s vaccine advisory committee and charge premium prices, they would likely need to demonstrate at least twice the benefit of standard flu shots, Dr. Arnold Monto, an influential influenza epidemiologist at University of Michigan School of Public Health, told STAT.
mRNA flu vaccine overview (does not include all hybrid flu/COVID vaccines)
| Company/Organization | Vaccine Name/ID | Description/Details | Phase & Study Details | Strains Covered (if specified) |
|---|---|---|---|---|
| Moderna | mRNA-1010 | An mRNA-based flu vaccine designed to elicit a robust immune response against flu strains. |
|
A/H1N1, A/H3N2, B/Yamagata, B/Victoria |
| National Institutes of Health (NIH) | H1ssF-3928 mRNA-LNP | An experimental universal influenza vaccine developed by NIAID’s Vaccine Research Center. |
|
Universal |
| Novavax | COVID-19-Influenza Combination Vaccine | Combination vaccine targeting SARS-CoV-2 and influenza using Novavax’s recombinant nanoparticle technology and Matrix-M adjuvant. |
|
|
| CureVac (with GSK) | Multivalent, modified mRNA seasonal flu vaccine candidate | mRNA-based seasonal flu vaccine candidate based on an advanced mRNA backbone. |
|
Broad coverage against WHO-recommended flu strains |
| Pfizer (in collaboration with BioNTech) | Quadrivalent modRNA influenza vaccine/COVID vaccine | mRNA-based influenza/COVID vaccine candidate with potential for rapid manufacturing, flexibility, and improved flu strain match. |
|
Strains recommended by WHO for the Northern Hemisphere |
| Sanofi and Translate Bio | MRT5400 & MRT5401 | Experimental mRNA-based influenza vaccine. |
|
Initial prototypes were more successful for A strains than B strains. |
| University of Pennsylvania | Multivalent mRNA vaccine | Experimental mRNA-based universal influenza vaccine targeting 20 strains. |
|
Universal |
Filed Under: clinical trials, Drug Discovery, Infectious Disease
