Good News On the Flu Vaccine Front

With all the news about COVID-19 vaccines recently, news about influenza vaccine research tends to get buried. However, research on flu vaccines continues and there is some good news to report.

Researchers have made progress in developing a universal flu vaccine that would work on most strains of the flu. It targets the stalk of the virus, an area that is common to all flu viruses and doesn't mutate often. 

Targeting the stalk is harder than it sounds, because immune memory cells built up over a lifetime of flu infections react so strongly to the conserved region of HA’s head that this response overrides production of antibodies against the stalk. Some researchers have tried to make flu vaccines that only contain HA’s stalk, but this fragment is highly unstable. To get around this problem, Krammer and colleagues made what they call chimeric HAs, which link the protein’s conserved stalk to unusual heads that are entirely new to the human immune system and don’t trigger a person’s immune memory. Only low levels of head antibodies are produced, allowing a strong new immune response to stalk to dominate. In essence, the head of the chimera is only there to stabilize the stalk.

Influenza vaccines contain three to four strains of the virus that are classified as group A, which breaks into two other divisions, and group B strains. The researchers developed vaccines made from live, weakened versions of influenza viruses or inactivated viruses bearing chimeric HAs representing only one division of group A. In the trial, 51 participants received the various vaccines and their antibodies were compared with those of 15 people who received placebos. A single shot of vaccine with chimeric HA inactivated viruses, the researchers report, “induced remarkably high antistalk antibody titers.”

The trial was only a phase I study to establish safety and measure immune responses, which means it didn’t test the ability of the vaccines to protect people from influenza. Still, when the researchers transferred human antibodies triggered by the experimental vaccines into mice and then “challenged” the rodents with the influenza virus, the mice lost far less weight than untreated mice who also were infected, suggesting the antibodies protected them. Immunologist James Crowe, who runs the vaccine center at Vanderbilt University, says the study is “a serious effort” to test the stalk antibody hypothesis and “an important first step.”

It will likely be a few years before such a vaccine can be put into widespread use. Hopefully it will come before we are faced with a serious influenza pandemic.