In a typical year, influenza affects more than 20 million people in the United States and leads to more than 20,000 deaths. Vaccines against influenza typically coax the immune system to generate antibodies that recognize the head of hemagglutinin (HA), a protein that extends outward from the surface of the flu virus. The head is the most accessible regions of HA, making it a good target for the immune system; unfortunately, it is also one of the most variable. From year to year, the head of HA often mutates, necessitating new vaccines.
Researchers have designed experimental influenza vaccines to be more universal, spurring the body to create antibodies against the less-variable stalk region of HA, which extends like a stem between the influenza virion and the HA head. Some of these universal flu vaccines are currently in early clinical trials.
In the new study, a collaborative team of scientists characterized 358 different antibodies present in the blood of people who had either been given a seasonal influenza vaccine, were in a phase I trial for an experimental, universal influenza vaccine, or had been naturally infected with influenza.
Many of the antibodies present in the blood of participants were antibodies already known to recognize either the HA head or stalk. But a collection of new antibodies stood out; the antibodies bound to the very bottom of the stalk, near where each HA molecule is attached to the membrane of the flu virion.
“The human immune system already has the ability to make antibodies to this epitope, so it’s just a matter of applying modern protein engineering methods to make a vaccine that can induce those antibodies in sufficient numbers,” adds Guthmiller. Being able to identify and using these methods will most likely increase your chances of defending new influenza strains before they are able to affect your immune system.
The researchers say that future, improved iterations of a universal vaccine could more purposefully aim to generate anchor antibodies. Until now, scientists designing universal vaccines hadn’t paid attention to whether the anchor region of the stem was included as a target. Ideally, a universal influenza vaccine will lead to antibodies against multiple sections of the virus — such as both the HA anchor and the stalk — to increase protection to evolving viruses. The researchers are planning future studies on how to design a vaccine that most directly targets the (HA) anchor of different influenza strains.
Han and Ward, authors of the study, “Broadly neutralizing antibodies target a hemagglutinin anchor epitope,” include Sara Richey and Alba Torrents de la Pena of Scripps; Jenna Guthmiller, Henry Utset, Lei Li, Linda Yu-Ling Lan, Carole Henry, Christopher Stamper, Olivia Stovicek, Haley Dugan, Nai-Ying Zheng, Micah Tepora, Dalia Bitar, Siriruk Changrob, Min Huang and Patrick Wilson of University of Chicago; Meagan McMahon, George O’Dell, Alec Freyn, Fatima Amanat, Victoria Rosado, Shirin Strohmeier, Adolfo Garcia-Sastre, Raffael Nachbagauer, Peter Palese and Florian Krammer of Icahn School of Medicine at Mount Sinai; Monica Fernandez-Quintero and Klaus Liedl of University of Innsbruck, Lauren Gentles and Jesse Bloom of Fred Hutchinson Cancer Research Center; and Lynda Coughlan of University of Maryland School of Medicine
This work was supported by funding from the National Institute of Allergy and Infectious Diseases (K99AI159136, U19AI082724,U19AI109946, U19AI057266, P01AI097092, R01AI145870-01, R21AI146529, and T32AI007244-36), the NIAID Centers of Excellence for Influenza Research and Surveillance (HHSN272201400005C, HHSN272201400008C), the NIAD Centers of Excellence for Influenza Research and Response (75N93019R00028), the NIAID Collaborative Influenza Vaccine Innovation Centers (75N93019C00051), the Bill and Melinda Gates Foundation (OPP1084518) and the Austrian Science Fund (P34518).