Moderna’s mRNA flu vaccine enters the clinic

The vaccine targets lineages recommended by the WHO for the prevention of influenza: including including seasonal influenza A H1N1, H3N2 and influenza B Yamagata and Victoria.

The Phase 1/2 randomized, stratified, observer-blind, dose-ranging study will evaluate the safety, reactogenicity and immunogenicity of mRNA-1010, Moderna’s seasonal influenza vaccine candidate in healthy adults 18 years and older in the US. Around 180 participants will be enrolled in the study.

Moderna is taking its successful COVID-19 mRNA tech into a range of new areas – including CMV, hMPV/PIV3, Zika and RSV (which are in clinical trials) and Nipah, EBV and HIV (in preclinical trials, with the HIV vaccine expected to move into clinical trials this year).

Another key area of development is creating a combo flu/COVID-19 vaccine: or other combination vaccines.

“We are pleased to have begun this Phase 1/2 study of mRNA-1010, our first mRNA seasonal flu vaccine candidate to enter the clinic. We expect that our seasonal influenza vaccine candidates will be an important component of our future combination respiratory vaccines,”​ said Stéphane Bancel, Chief Executive Officer of Moderna.

“Respiratory combination vaccines are an important pillar of our overall mRNA vaccine strategy. We believe that ​the advantages of mRNA vaccines include the ability to combine different antigens to protect against multiple viruses and the ability to rapidly respond to the evolution of respiratory viruses, such as influenza, SARS-CoV-2 and RSV. Our vision is to develop an mRNA combination vaccine so that people can get one shot each fall for high efficacy protection against the most problematic respiratory viruses. We look forward to advancing our core modality of prophylactic mRNA vaccines so that we can continue to make an impact on global public health.”​

Egg-based vaccines vs mRNA tech

While Moderna demonstrated its first mRNA-LNP vaccine proof of concept back in 2013, it has of course been the coronavirus pandemic that has propelled the tech into the limelight with the first authorization of mRNA-1273 in December 2020.

In its Vaccines Day earlier this year, Moderna described its mRNA vaccine tech as a ‘large commercial opportunity’ – with the vaccine market large and growing (estimated at $35bn in 2020).

It sees two main paths for growing in this market: with new vaccines against viruses for which there are no vaccines on the market (such as HIV); or new vaccines to improve the efficacy and/or safety of currently approved vaccines (such as the flu vaccine).

Seasonal flu (type A and type B) epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing substantial burden on healthcare systems. The WHO estimates approximately 3-5 million severe cases of flu each year globally, and 290,000-650,000 flu-related respiratory deaths.

In the US alone, the estimated average economic burden of the flu is around $11bn a year: with around 8% of the population experiencing symptoms of flu.

So how could mRNA vaccines help? Current flu vaccines in the market have efficacy rates in the region of 40-60%: which Moderna believes its mRNA technology can improve on (its COVID-19 vaccine mRNA-1273 has an efficacy rate of 94.1%).

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).

There is also a long lead time for vaccine strain selection and development of current vaccines (formulation of vaccines must be decided 6-9 months before they are used); and delays in availability when strains are updated.

Moderna, therefore, sees the opportunity to use its mRNA tech to create influenza vaccines with improved and longer lasting efficacy; and vaccines that can be developed and manufactured more quickly to provide a better match to circulating strains of the time.

Moderna hasn’t put figures on how long either a flu or COVID-19 vaccine could be redeveloped against new variants; but it does highlight that the advantage of an mRNA platform is that set up and production remains the same. Changes to a vaccine would be relatively minor and only affect the mRNA itself.  Meanwhile, fellow mRNA pioneer BioNTech has suggested that vaccines against new COVID-19 strain could be developed within six weeks if needed:​​ with scale-up of mRNA production far quicker and slicker than growing virus in eggs.

And Moderna adds that having another tech available for influenza vaccines would help boost pandemic preparedness against flu: whether in terms of quantity and speed or in the eventuality that a new influenza strain does not grow well in eggs.