Medical Research: Monique Ambrose: Influenza pandemics pose a serious, recurrent threat to human public health. One of the most probable sources of future pandemic influenza viruses is the pool of influenza A virus (IAV) subtypes that currently circulate in non-human animals. It has traditionally been thought that the human population is immunologically naïve and unprotected against these unfamiliar subtypes. However, our work suggests that an individual ‘imprints’ to the influenza A virus (IAV) encountered in early childhood in such a way that they retain protection against severe disease if they later encounter a novel IAV subtype that belongs to the same genetic group as their first exposure.
Our research looked at human cases of H5N1 and H7N9, two avian IAV
subtypes of global concern, to investigate what factors most strongly
predicted risk of severe disease. The most striking explanatory factor
was childhood IAV imprinting: our results suggest that individuals who
had childhood imprinting on an IAV in the same genetic group as the
avian IAV they encountered later in life experienced 75% protection
against severe disease and 80% protection against death.
MedicalResearch.com: What should readers take away from your report?
Monique Ambrose: We’ve found striking
real-world evidence that the subtype of influenza you’re exposed to in
early childhood affects how sick you get when you’re exposed to a new
strain of influenza
that you’ve never encountered before. This has very relevant
implications for managing our resources during the next influenza
pandemic. We can predict which groups of people are at greater risk of
experiencing a severe or fatal infection and which groups are most
likely to have some protection from protective childhood imprinting.
This can help us determine how to distribute vaccines or otherwise
target our control actions.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Katelyn M. Gostic: There are a number of needed follow-up studies.
First and foremost, while our study clearly demonstrates the
population-level consequences of childhood HA imprinting, the specific
immune mechanism responsible for these patterns remains unknown. We
proposed a number of promising candidate mechanisms in the published
manuscript, but we are still working with laboratory scientists and
immunologists to test these hypotheses.
On a similar note, we are not yet sure if HA imprinting protection
prevents infection entirely, or merely reduces the severity of infection
in protected individuals.
MedicalResearch.com: Is there anything else you would like to add?
Katelyn M. Gostic: One interesting aspect of
this research is its potential relevance to the 1918 influenza pandemic,
which infamously killed huge numbers of otherwise healthy 20-30
year-olds. Why the 1918 pandemic was so deadly, and why it
disproportionately affected young adults is one of the great mysteries
in epidemiology, and has still not been fully resolved. The HA
imprinting patterns examined in our study actually grew out of an idea
put forward by senior author Dr. Mike Worobey, which says that
mismatched (group 2) childhood imprinting among the 20-30 year-olds of
1918 may explain why this group suffered so much mortality from the 1918
(group 1) pandemic strain.