In preparation for the upcoming flu season in the Northern Hemisphere, companies like Sanofi Pasteur are preparing to deliver the first batches of vaccines against the potentially deadly virus. Over the coming months, as the flu circulates, hundreds of millions of people around the world will be immunized against the strains of the virus that global health authorities have forecast will be most prevalent this year.
Public health authorities, physicians and the public all hope the forecast – made about six months ago – is on target. Nobody wants a second flu season like the last, where unexpectedly virulent strains rendered the vaccine less effective than normal, leading to infection rates that public health officials in the U.S. called the worst in a decade.
What everyone really wants is not simply better forecasts, but instead a new kind of vaccine, one that is more effective against a far broader range of flu strains. That would be a major step toward defeating what remains one of the most dangerous viruses affecting humans.
Exactly 100 years ago, the 1918 flu pandemic saw 500 million people infected and an estimated 50 million to 100 million deaths. Since then, vaccination and other public health measures have vastly improved, but according to the World Health Organization (WHO) there are still between three and five million serious cases of the flu worldwide each year, with those infections resulting in as many as 650,000 deaths.
The flu is particularly dangerous to infants, the elderly and people with weakened immune systems. Even if it isn’t fatal, a case of the flu often can require emergency care or hospitalization. That’s why public health authorities consider immunization such an important tool and why researchers are hard at work on better vaccines with broader protections.
“Last season may not have been 1918, but it was very serious,” said John Shiver, Ph.D., Senior Vice President, Global R&D, Sanofi Pasteur. “As long as the flu has such devastating potential, we have to keep applying the latest knowledge and the advances in both bioscience and information technology to help develop more effective ways to help prevent infection and possible epidemics.”
Producing seasonal flu vaccine is a year-round commitment for Sanofi Pasteur. The company produces 200 million doses of flu vaccine every year to help meet public health needs around the world, which is a massive undertaking. While newer production methods currently used by Sanofi Pasteur and other companies have expanded capabilities to make additional flu vaccine doses, they have not significantly shortened the overall production timeline it takes each year.
Vaccinating Against a Complicated Foe
One of the biggest challenges for vaccine makers – and one of the public’s most common misconceptions about the flu – is that it is not a single virus. Influenza occurs in numerous variations, or strains, some of which are typically more virulent than others. In addition, the strains that are most prevalent and therefore, the most likely to infect, tend to change every flu season.
The traditional flu vaccine, like most vaccines against viral infections, relies on the natural responses of the human immune system. A dose of vaccine contains inactivated viruses that cause the immune system to generate antibodies that attach to active virus particles and can either render them inactive or help destroy them.
Each year, the WHO along with public health officials use the Global Influenza Surveillance and Response System (GISRS) to attempt to predict the four variants that will be most prevalent and virulent for the coming flu season. Vaccine makers use those selected strains to manufacture a matching vaccine.
Forecasting which versions of the virus are likely to be most prevalent in the coming flu season isn’t a perfect science, however. Sometimes the flu cooperates, and the vaccines are highly effective. In other seasons, such as the most recent one, the circulating virus is less susceptible to the vaccines available on the market. As a result, people may get the flu despite having gotten a shot.
While producing flu vaccine is a year-round process for Sanofi Pasteur, it’s also a time-consuming one. That makes getting the predictions correct important, because vaccines they need to be made several months in advance to allow time to produce enough doses.
Even using newer techniques for growing the flu virus, the overall process to bring the vaccine to patients is not much faster, because of the time required to test the new vaccine for quality before doses can be made available to health care providers to administer.
Even if those forecasts are accurate, there’s still an issue when it comes to how effective the vaccine can be.
The flu, it turns out, is also crafty.
As the virus replicates, it can undergo what scientists call “antigenic drift,” which creates small changes in its genes. It’s a survival mechanism for the virus, but the same mechanism can also render traditional vaccines ineffective. That’s because the changed virus is no longer recognized by the antibodies the vaccine has generated in the body.
Striving for a Better Flu Vaccine
Eventually, the dream of patients and scientists alike is for a universal flu vaccine that would protect against every iteration of the virus, in a single treatment. That’s one of the most sought-after discoveries in the field of influenza immunization, but also a development that most researchers believe is a decade or more away and will require the development of a host of new technologies.
What’s most likely to happen before then is continued improvements in existing vaccine technology, as well as a broadly protective influenza vaccine (BPIV). BPIV would combat a wider range of virus strains and would also help the body produce antibodies against them for a longer period of time.
Scientific research of any new technology, however, takes time. Understanding the potential benefits newer technologies may have on a vaccine’s performance requires years of study. Our experts know this firsthand, as they aggressively pursue a BPIV research program, which will take years to research in clinical studies.
So it is important that until new flu vaccines are developed beyond the lab and fully studied and brought to market, we continue to educate providers about the benefits of existing flu vaccine options.
The long road to a universal vaccine
Even an effective BPIV option won’t be the final knockout punch against the flu, which is why researchers are working hard to develop a “universal” vaccine that would provide long-term protection against the flu in all its forms.
But given the fact it would have to be effective against most or all variants of the virus at once, the current methods for vaccine production won’t work. So an entirely new technology is needed that can be effective across far more variants.
A universal vaccine would have to be able to account for this shift, which is highly unpredictable. Currently, it is hard to target all the basic variants that make the entire problem that much more challenging.
That’s one reason the most recent U.S. federal spending bill set aside $100 million of an increased NIH budget toward the task, while some lawmakers have called for spending as much as $1 billion on the problem over the next five years.
Until a newer vaccine becomes available, the traditional vaccine is still an immensely important public health tool. Regardless of the forecast for the season, getting a flu shot is still the most effective preventive measure one can take.
“While a lot of people may think of the flu as just making life unpleasant for a few days, it is an extremely serious and dangerous illness, even a life-threatening one,” said David P. Greenberg, M.D., Associate Vice President and Regional Medical Head North America, Sanofi Pasteur. “The elderly, children and others with weaker immune systems can be severely affected, and even healthy adults can become extremely sick. Even in the most severe flu seasons, vaccines still prevent millions of cases of the flu.”
Even in a severe season like 2017-2018, the vaccine will still offer protection for millions of people against a virus that has a lot of tricks up its sleeve.