A Look Inside Influenza Vaccines: Today And Tomorrow

Published on: February 20, 2019


At the height of the flu season, headlines often claim “next generation” or “new and improved” influenza vaccines.  When it comes to innovations in public health, however, it’s important to understand what’s behind the headlines so that health care providers and their patients can make informed decisions about influenza prevention.  Let’s look at why effectiveness of different influenza vaccines can vary today and how Sanofi Pasteur, Sanofi’s vaccines business, is seeking to further improve protection against the flu in the future.

What egg-vs-cell really means

In recent flu seasons the WHO, US FDA and vaccine manufacturers have focused in on how influenza vaccines are produced because this factor may influence vaccines’ efficacy.  For the majority of influenza vaccines, scientists insert an influenza virus into either chicken eggs or cell culture (a medium derived from animal tissue). In both cases, the virus replicates over and over. This forms the basis for the main ingredient for influenza vaccines (the antigen).   A flu vaccine cannot cause flu but “trains” your immune system to recognize and better combat a live virus when encountered in the environment. Regardless of the production medium, strictly sterile manufacturing procedures take months and include purification, quality testing, safety controls, packaging and regulatory verifications and releases, among other steps.

For more than 70 years, we could only produce influenza vaccines this way in eggs and egg-based production remains the only way to supply enough volume to meet worldwide public health needs. At Sanofi Pasteur, we are the leading influenza vaccine producer, delivering nearly 200 million vaccines, 40% of all doses worldwide, each year; the large majority of these are produced in eggs. 

Manufacturing vaccines by growing influenza virus in cells is a more recent addition to supplies, first coming to market in the last decade.  But so far, the jury is still out on whether producing vaccines in this way in cells provides any significant benefits each and every year, versus producing vaccines in eggs. The data is not yet comprehensive enough to demonstrate whether one manufacturing approach over another improves protection against the flu consistently year after year. 

In addition, it’s important to note that so far, total cell-based manufacturing accounts for only a small portion of worldwide supply; a fair estimate based on manufacturers’ limited reporting would put it at less than 15%, leaving a huge portion of public health needs unsatisfied. Protecting public health today and in the future requires confidence in all influenza vaccines, regardless of how they are produced.  For these reasons, our industry also has a responsibility to communicate ethically and in balanced way around availability, efficacy and impact of each type of vaccine.  

New technology carves a third path

The problem with influenza virus replication is that it leaves room for mutations: the virus can shift and change in the eggs and cells as it replicates, sometimes leading to disparities with the viruses circulating in the population.  This is one of the factors that can negatively impact influenza vaccine efficacy.

One of Sanofi Pasteur’s newest vaccines uses recombinant technology – i.e. technology that replicates only the portion of the virus’ genetic makeup necessary to prevent flu – we don’t rely on the influenza virus replicating itself.  Our hope and expectation is that the use of such technology may help to avoid mutations.  

A broadly protective influenza vaccine

We believe that this recombinant vaccine technology can also serve as the core of a different kind of vaccine in the future: a shot that offers protection against a wide variety of influenza virus strains, not just those anticipated to circulate in the season ahead.  That could mean that this “broadly protective influenza vaccine” can be the basis for highly effective prevention year after year, and we avoid the variation in efficacy that is reported for current flu vaccines. 

In the meantime, as an industry, we must continue to communicate responsibly about the importance of flu vaccination as a whole.  While comparative effectiveness research is important, we should continue to communicate about research results in ways that take a holistic look at different vaccine options, patients’ profiles and best clinical outcomes over time. 

Beyond egg-vs-cell, there are in fact many options out there for people seeking to best protect themselves and their families.  From high dose vaccines (produced in eggs) that have more antigen content than standard doses, to recombinant technology based vaccines, standard dose vaccines (produced in eggs or in cells): it’s critical to help reduce the risks associated with influenza with effective and available vaccines for anyone who chooses to be vaccinated. 

The importance of the egg

For vaccine production, the egg remains the most reliable method for rapidly manufacturing large volumes of well tolerated and effective influenza vaccines and responding to global needs. It meets perfectly the flexibility and adaptability required for the vaccine’s manufacture. Nevertheless, for the future, we are exploring new options, including cell production, with the recent acquisition of Protein Sciences, a biotechnology company that has developed the only recombinant protein-based influenza vaccine. This technique will be an alternative that could replace the egg that, for now, remains obligatory.


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