Developing vaccines to prevent a devastating flu pandemic

A newly emerging influenza that causes large-scale severe illness is the greatest pandemic threat to humankind — not a coronavirus — with some models estimating that nearly 33 million people could die within the first six months of the onset of this type of pandemic, according to health experts.

“The question is not ‘if’ we will have another influenza pandemic, but ‘when,’” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, during a press conference last Thursday.

Even without a severe pandemic, influenza — a highly contagious respiratory virus — kills up to 650,000 people every year, causing serious illness that causes hospitalization in about 5 million and can increase the risk of a heart attack or stroke.

But currently, seasonal vaccines for influenza have limited overall effectiveness and their production is too slow. And there are significant gaps in knowledge around how flu viruses change and how to create durable immune responses. To address this and increase investment in influenza vaccine development, a group of experts launched a 10-year research and development road map last week.

“Current influenza vaccines are nowhere near as effective as they need to be, with overall effectiveness ranging from 10% to 60%,” Osterholm said, in a press release.

For many low- and middle-income countries — flu vaccine campaigns are simply not worth the cost, given the limited efficacy and need for health workers to administer them to the same people each flu season, said Martin Friede, coordinator for the Initiative for Vaccine Research at the World Health Organization.

“For many countries in low resource settings, they look at this and say: Well, that's too much for us to invest in,” Friede said. “However, in these countries, there is a significant burden of influenza, causing hospitalization and causing deaths.”

“For these populations, we need better vaccines; we need vaccines that protect for a longer period of time; and that we don't have to vaccinate every single year,” Friede said.

The holy grail for researchers is a broadly protective, universal vaccine, which would provide long-term protection against all influenza viruses, ending the need for seasonal vaccinations, and prepare the world for a pandemic.

But with both the development of seasonal and universal vaccines, there is a lack of coordination around vaccine research efforts, experts say.

“We believe that this lack of coordination and prioritization has been one of the barriers to moving the field of influence of vaccines forward,” said Charlie Weller, head of vaccines at Wellcome.

The development of seasonal influenza vaccines is based on an outdated, time-consuming technology developed in the 1940s where vaccine strains are grown in chicken eggs. Because it is a slow and unreliable process — the global health community must forecast far in advance what the dominant influenza strains will be during a season in order to ramp up development and production, but these predictions can be wrong.

“This is an incredibly inappropriate technology for us to be using in the 21st century,” Friede said.

To encourage political commitment, investments, and create new partnerships in vaccine development, a consortium of flu experts launched a 10-year master plan detailing how the global community could reach the goals of improving the effectiveness and quicken the pace of production of strain-specific seasonal influenza vaccines, as well as advance the development of universal influenza vaccines.

“If we embrace it, we could potentially tame seasonal epidemics and prevent and rapidly mitigate a potentially devastating influenza pandemic,” Osterholm said.

The road map was developed by the Global Funders Consortium for Universal Influenza Vaccine Development, Wellcome, Center for Infectious Disease Research and Policy at the University of Minnesota, WHO, the Sabin Vaccine Institute, the Bill & Melinda Gates Foundation, and the Task Force for Global Health.

The road map calls for a better understanding of a durable immune response to influenza and of the changes occurring in the viruses as they circulate in humans and animals around the world, as well as the ability to identify new viruses with pandemic potential.

It calls for the improvement in the use of animals in research to better reflect human responses. The road map also calls for trials with human participants. While there are currently many universal influenza vaccine candidates under development, clinical trials are challenging because they must span multiple seasons and different viruses. The road map calls for the harmonization of protocols.

It also calls for more rapid production of seasonal vaccines, which would mean that vaccines can be produced closer to the influenza season, and for communication and advocacy strategies to better articulate the benefits of developing improved vaccines for influenza.

“We really don't want the road map to be a document that sits on a virtual shelf. We want it to be used; we want it to be useful to those influenza [research and development] communities and to guide and focus research in this area,” Weller said.

Visit the Building Back Health series for more coverage on how we can build back health systems that are more effective, equitable, and preventive. You can join the conversation using the hashtag #BuildingBackBetter.