Insights into influenza through human challenge



Influenza continues to kill thousands of Americans each year. Although flu vaccines are available, the protection they provide can be incomplete and the vaccine must be re-developed each year to defend against current circulating strains. In the absence of human challenge studies, the induced immune response (antihemagglutinin (HA) antibody) used to evaluate seasonal vaccines has not been examined since the 1970s.


IRP researchers led by Matthew Memoli, M.D., M.S., successfully developed and implemented the first influenza challenge study in healthy volunteers in the U.S. in over a decade. In this study, doctors exposed individuals to a flu virus and then studied their immune responses to better understand how flu makes us sick, how we best recover, and how to develop better therapies and broadly protective vaccines. Through this approach, researchers demonstrated for the first time that antineuraminidase (NA) antibody titer is more accurately and independently predictive of flu protection and reduced disease than the previous gold standard of HA antibodies.


With antineuraminidase (NA) antibody titer as a more accurate indication of flu protection, we may soon be able to develop more effective annual flu vaccines. Development of the influenza challenge model greatly facilitates testing of novel universal broadly protective vaccine candidates, therapeutic approaches, and diagnostic techniques that could have a significant impact in reducing influenza morbidity and mortality.  Moreover, the model generated considerable data on components of human flu response that may lead to the development of a universal influenza vaccine.


Memoli MJ, Shaw PA, Han A, Czajkowski L, Reed S, Athota R, Bristol T, Fargis S, Risos K, Powers JH, Davey RT Jr, Taubenberger JK. (2016). Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model. mBio. 7(2).