Flu vaccines have been made in the same way for nearly 70 years: based on growing the flu virus in chicken eggs or mammalian cells, which is then inactivated and processed to be made into vaccines.
The disadvantage of this approach is there can be much variability in the finished product – the virus can mutate during vaccine production – and the production process must be updated for every new strain.
The manufacturing process for the RNA vaccine is also simpler that the current vaccine technology. At research scale, Pfizer estimates RNA vaccine can be made eight days after the sequence of a new flu virus is first known.
Pfizer’s mRNA flu vaccine – also in partnership with BioNTech but started in 2018 before the companies’ COVID-19 collaboration – is set to enter human trials this month, said Frank A. D’Amelio, Pfizer CFO and executive VP of global supply, at the Morgan Stanley 19th Annual Global Healthcare Conference this week.
“Current vaccines for flu provide 40% to 60% protection,” said D’Amelio. “And it can be lower than that in vaccine years where there's a poor matching of the strains, right, because it's all about the matching of the strains when it comes to flu.
“So we think if we can provide a vaccine that provides much more protection, and when we can do more timely manufacturing of the known strains, that combination of that better manufacturing… [and]… strain knowledge manufacturing… we think that could provide much greater protection to patients relative to the flu.
“So we think there's a significant opportunity here for patients and obviously for ourselves. We expect to begin a first-in-human trial of a quadrivalent flu vaccine by the end of September, by the end of this month."
Moderna
Moderna, meanwhile, is working on mRNA-1010: a quadrivalent seasonal influenza vaccine targeting WHO recommendations including A H1N1, H3N2 and influenza B Yamagata and Victoria lineages.
Last week it announced that a Phase 1/2 study for the candidate is now fully enrolled. The study is assessing three different dose levels of mRNA-1010 in adults ages 18-49 years and above 50 years
The company has also set out plans for a new development candidate, mRNA-1073, which would be a combination COVID-19 booster and seasonal flu booster vaccine.
Translate Bio
In June, Sanofi and Translate Bio (which Sanofi acquired this week) started a Phase 1 clinical trial for their mRNA influenza vaccine.
Interim data is expected by the end of 2021.
The monovalent flu vaccine candidate codes for the hemagglutinin protein of the A/H3N2 strain of the influenza virus (Sanofi notes that flu seasons dominated by A/H3N2 strain tend to be more severe, especially among those considered at-risk such as older adults and younger children.)
Sanofi and Translate Bio have developed and will evaluate two formulations of the vaccine (MRT5400 and MRT5401) in the Phase 1 influenza mRNA vaccine clinical trial. The two formulations differ in the lipid nanoparticle (LNP) that contains the mRNA. The US trial will assess the safety and immunogenicity of the candidate in up to 280 participants aged 18-49 years old.
The candidate is not far behind their mRNA COVID-19 vaccine candidate: which started a Phase 1/2 trial in March.
Next generation mRNA
Meanwhile, CSL business Seqirus is working on a next-generation mRNA vaccine, using self-amplifying messenger RNA (sa-mRNA). The company is targeting commencement of clinical trials for both seasonal and pandemic influenza vaccine candidates in the second half of 2022.
mRNA vaccines help protect against infectious diseases by giving instructions to cells in the body to create the protein for the immune response to fight. Self-amplifying mRNA - ‘the next generation version of today’s mRNA technology,’ - also instructs the body to replicate mRNA, amplifying the amount of protein made.
This could enable vaccine manufacturers to potentially develop more effective vaccines with a smaller dosage and with lower rates of reactogenicity, says Seqirus.