Background
Identification of correlates of protection against human influenza A virus infection is important in development of broadly protective (“universal”) influenza vaccines. Certain assumptions underlie current vaccine developmental strategies including that infection with a particular influenza A virus should offer long term or lifelong protection against that strain, preventing reinfection. In this study we report observations made when 7 volunteers participated in sequential influenza challenge studies where they were challenged intranasally using the identical influenza A(H1N1)pdm09 virus approximately 1 year apart. We evaluate and describe the outcomes of these seven re-challenge participants and discuss what these results may suggest about correlates of protection and development of more broadly protective influenza vaccines.
Methods
Seven participants were enrolled in two viral challenge studies at 7.5 to 18.5 month intervals. Both challenge studies used the identical lot of influenza A (H1N1)pdm09 virus administered intranasally. We evaluated pre- and post-challenge HAI, NAI, and stalk antibody titers, peripheral blood leukocyte (PBL) host gene expression response profiles, daily viral detection via nasal wash, and clinical signs and symptoms.
Results
At least 3 of 7 participants demonstrated confirmed laboratory evidence of sequential infection with 5 of 7 demonstrating clinical evidence.
Conclusion
The data presented in this report demonstrate that sequential infection with the identical influenza A virus can occur and suggest it may not be rare. These data raise questions about immune memory responses in an acute superficial respiratory mucosal infection and their implications in development of broadly protective influenza vaccines. Further investigation of these observations is warranted.