Additional teams are focusing on completely different strategies, such as designing a vaccine that encourages the production of T cells, the attack dogs of the immune system. T cells produce broader, longer-lasting immunity than antibodies, but classic flu vaccine formulas do not encourage their activity. Others are administering a sequence of vaccines against different flu strains so that the immune system assembles a diverse antibody artillery.
Much of this research has happened only in the past five years. In fact, for 15 years after the earliest studies in Japan, work on a universal flu vaccine accumulated in mere dribs and drabs—until a pandemic, which killed more young and middle-aged adults than usual, jolted scientists into a higher gear. In April 2009 a highly infectious new strain of swine virus dubbed H1N1 jumped suddenly from pigs to people. Manufacturers had already spent months preparing the vaccine for the 2009–2010 season, which was still a ways away—and that vaccine was useless against the new strain. They had to go back to square one.
Beginning work on the H1N1 vaccine so late in the manufacturing cycle, combined with some peculiarities of the virus—it was not easy to replicate en masse in the lab, which slowed down production—resulted in millions of doses arriving on the market months after planners hoped. By the next spring, H1N1 killed as many as 18,000 people in the U.S. These delays spurred some incremental changes in flu vaccine manufacturing. Yet they also underscored the fact that better techniques cannot solve the root problem of having to rapidly fabricate a new vaccine every time a completely new virus appears.
“We realized that despite all the technology we have, it is very hard to manufacture and deliver a [brand-new] vaccine in time to actually have an impact,” says Kanta Subbarao, chief of the emerging respiratory viruses section at the NIH.
Even if researchers who are working on a universal flu vaccine finally overcome all their remaining technical challenges, the real hurdle may be securing both funding for future studies and federal approval for a new product. Asked what he needs to begin trials with people, Peter Palese, who is a professor and chair of microbiology at Mount Sinai Hospital in New York City, laughs and replies, “Money.” Federal or private money? “Any money,” he says.
His answer captures the paradox of research into new flu vaccines. Although current vaccines are flawed and require a lot of time to tweak, they confer some protection most of the time. “Why expend the effort to invest hundreds of millions of dollars to get to something new?” says Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, which published a lengthy 2012 report scrutinizing the lack of private and government funding for “game-changing” flu vaccines.
Certain unique properties of the most promising universal flu vaccines in production may be a source of additional obstacles. Studies have suggested that the experimental universal flu shots do not trigger as strong an immune response as older vaccines do. Guaranteeing that the new vaccines are as effective as the old ones may mean adding more ingredients or finding new ways to administer them.
Any new flu vaccine is practically guaranteed lengthy FDA examination. Current seasonal vaccines change so little from year to year that they move through FDA review quickly. But a universal vaccine—using new antigens and a new delivery system—would undergo extensive inspection for both efficacy and safety. For comparison, approval of the vaccine Prevnar, the first to confer protection against pneumonia in infants and young children, took 15 years and required very large clinical trials. “There are 60, 70 years” of FDA approvals and clinical experience behind existing flu vaccines, Palese points out. “But if you go in with a new approach, then the FDA will be starting from zero as well.”