While it is the best tool we have to fight influenza virus infection, the efficacy for the influenza vaccine can clearly be improved. To date, strategies have included using more viral antigen (i.e., “high-dose” influenza vaccine) or adding an immune-enhancing adjuvant (i.e., squalene). Although these vaccines appear to be somewhat better than their more traditional counterparts, the problem with finding an influenza vaccine that induces high-level, broadly cross-reactive protection against challenge remains.
Recently, however, investigators in China developed a novel strategy (Du Y, Xin L, Shi Y, et. al., Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design. Science. 2018; Jan 19;359(6373):290-6; and Teijaro JR and Burton DR. Taking down defenses to improve vaccines. Science 2018 Jan 19;359(6373):277-8).
One strategy that influenza virus uses to gain an advantage on the host is to suppress the production of type 1 interferons by the immune system. By suppressing the body’s natural defense against viral invasion, the virus gains a replication advantage. Investigators seized on this observation to create a strain of influenza virus that was at once incapable of suppressing type 1 interferons while at the same time was hypersensitive to the production of interferons. This hyper-interferon sensitive (HIS) virus reproduced itself well in vitro, but was highly attenuated in interferon-competent experimental animals. Better yet, the virus induced high levels of broadly cross-reactive T and B cell responses.
It will be interesting to see what happens when these HIS strains are tested in people. But this novel strategy certainly has promise.