At present, several companies, including Moderna Inc (MRNA.US), Pfizer Inc (PFE.US) / BioNTech (BNTX.US), Sanofi (SNY.US) / Translate Bio (TBIO.US) and GlaxoSmithKline PLC (GSK.US) / Curevac (CVAC.US), are promoting the clinical project of influenza vaccine based on mRNA technology. In the best scenario, the monovalent influenza vaccine may enter the market in 2023, while the combined vaccine is expected to be available after 2024.

Although the mRNA research and development project is still in its early stages, it is worth noting that global suppliers of large flu vaccines are pushing forward their efforts in a market with Goldman Sachs Group's estimated size of more than $6 billion.

The overall vaccination rate in developed markets is 30-50 per cent, in part because the current effectiveness of vaccines is between 20-60 per cent. The technology of replicating viruses from eggs still dominates vaccine production, but the recent rise of technologies based on cell and recombination methods shows the industry's pursuit of innovation. The global number of vaccinations reached 5.5 billion doses in 2019, of which seasonal influenza vaccine is the fourth largest category, accounting for more than 500 million doses (it is worth noting that this will be far less than the COVID-19 vaccination dose in 2021). As a result of the increased demand due to the epidemic, we expect the market for influenza vaccines to exceed US $6 billion in 2021.

The development and verification of mRNA vaccines has made rapid progress in the past 18 months, which raises a series of new issues for current influenza vaccine manufacturers. The development of influenza vaccines using mRNA technology is expected to provide the following advantages: 1) efficacy; 2) speed; and 3) flexibility.

Potential advantages of mRNA over traditional vaccine production

Three factors give mRNA technology the potential to bring about disruptive changes in the traditional vaccine market:

1. Efficacy

High biofidelity: mRNA can be correctly transcribed into an ideal protein.

The ability to achieve complex antigen / multivalent: the mRNA sequence encoding different viral proteins can be incorporated into a single vaccine to promote the production of complex polymer antigen, but it is difficult for traditional vaccines to do this.

Ability to produce combined preparations / co-preparations (co-formulation): several companies are exploring the development of combined vaccines.

The expected effectiveness is high: the effectiveness of the current influenza vaccine is only 40-60%, and its formula is determined 9 months ahead of the expected use time of the vaccine. Some vaccine manufacturers say that mRNA technology can help vaccinators produce a strong immune response (neutralizing antibodies and T cells) and improve the matching of influenza vaccines with the sequences of influenza strains that are spreading, bringing significant improvements to currently available influenza vaccines.

Mitigate the risk of antigenic change or drift: the use of eggs for vaccine production may also bring unexpected antigenic changes to the vaccine virus.

two。 Speed

Reduced production / approval time: mRNA is a platform technology that can complete the process of prophylactic vaccine from "sequencing", "clinical" to "approval" in a relatively short period of time.

Rapid research and development process: the virus strain targeted by the current vaccine does not match the virus strain that is spreading, which brings great challenges to the effectiveness of the current influenza vaccine.

3. Flexible production process (cell-free process)

No need for specialized factories: manufacturers may have greater flexibility in production because they may transition from producing mRNA vaccines to producing mRNA therapeutic agents based on the same process.

Cell-free manufacturing process: some mRNA technology advocates (such as Moderna Inc) use cell-free methods (in vitro transcription) and proprietary purification techniques to develop mRNA drugs free of immune-activating impurities, and are consistent throughout the R & D pipeline.

Potential disadvantages of mRNA Vaccine

Reactivity: although most are mild to moderate, mRNA vaccines may cause strong reactive symptoms (such as fever, chills, fatigue and headache), especially after a second dose, which may interfere with daily activities, including work. At present, the trade-off between risk and benefit of COVID-19 epidemic is very convincing from both individual and social point of view. However, for younger or healthy people, the same risk and benefit measure may not be applied to influenza vaccine.

Myocarditis and pericarditis risk: following the most recent expert group meeting of the Centers for Disease Control and Prevention (CDC) / Advisory Committee on Immunization practices (ACIP), the US Food and Drug Administration (FDA) has updated the Pfizer Inc / BioNTech and Moderna Inc COVID-19 Vaccine Emergency use Authorization pages To include hints about a potentially increased risk of myocarditis and pericarditis, especially after a second dose.

Problems with pre-existing immunity: one of the urgent problems is the problem of antigens transferred to different immune platforms (that is, the body's response is driven by previous immune system memories / antigens, rather than relying on new antigens). The problem here is that the redesigned vaccine only promotes the response of primitive neutralizing antibodies, not leads to a new set of antibodies against new variants of the virus. In this regard, seasonal flu is different from COVID-19 because most people have been vaccinated against COVID-19 for the first time.

Overall, the main advantage of mRNA over traditional production methods is that it can develop a vaccine more quickly (in weeks rather than months) after the identification / sequencing of the relevant virus strains, so it is expected to significantly improve the matching of the vaccine and the virus. Although there are still many questions to be answered about the application prospect of mRNA technology in the field of influenza vaccine, since the last major innovation in the field of vaccine-the technology of virus replication using eggs-was first commercialized more than 70 years ago, mRNA technology undoubtedly provides the possibility to achieve important innovation in this field.

This article is edited from Goldman Sachs Group GoldmanSachs, author: Goldman Sachs Group; Zhitong Financial Editor: Wei Haoming.