On Nov. 19, 2019, Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, happened to be describing to me recent research that was on his mind. “A real hot topic” at that moment, he said, was the development of a universal influenza vaccine. He meant a vaccine suitable for all ages that would be at least 75 percent effective for a year or more against Influenza A viruses — the type that causes pandemics but that also, along with Influenza B, annually infects as many as a billion people worldwide and kills somewhere between 290,000 to 650,000 of them. A push to develop such a vaccine began in earnest about a decade earlier and was gaining momentum. “That’s something that I’m spending a lot of time on,” he said. “Also, a lot of scientists are struggling in a positive way to make advances.” It was, he went on, “somewhat embarrassing” that a new and updated flu vaccine had to be made every year. “We really need to do much, much better to get a better vaccine. One that covers all of the possible iterations of influenza.”
Last month, two years and a coronavirus pandemic later, I asked him if in late 2019 he would have guessed that an influenza virus would be the cause of the next pandemic. “Yes, of course,” he said. “They would say, ‘What’s your worst nightmare?’ and I would say, ‘It would be the emergence of a brand-new virus likely jumping from an animal species to a human that’s respiratory-borne, and that most likely would be influenza.’” And “the next one might be,” he added.
Novel influenza viruses that leap from birds or pigs to people have caused four pandemics in a little over a century; the one in 1918 is believed to have killed 50 million people. When enough of the global population gained some immunity to those viruses through exposure or vaccination, they faded away or became seasonal. (Many believe SARS-CoV-2 will eventually become endemic as well, circulating at low levels like the coronaviruses that cause the common cold.)
Part of the reason the influenza virus has proved impossible to eradicate has to do with its structure. The surface of all influenza strains is studded with proteins, the most important of which, for Influenza A and B, are hemagglutinin (HA) and neuraminidase (NA). (The nomenclature of viral strains like H1N1 describes their varying combinations.) The HA proteins have a thin stalk and a rounded head, like a lollipop. The head is the part of the protein that binds to our cells, whereas the stalk contains the machinery to fuse the viral and cell membranes, making possible the transfer of genetic material. The HA head tends to be the structure our immune system — on its own or prompted by a vaccine — recognizes as an invader and for which it produces neutralizing antibodies.