Adenoviral vaccine induction of CD8+T cell memory inflation: Impact of co-infection and infection order

The efficacies of many new t cell vaccines rely on generating large populations of long-lived pathogen-specific effector memory cd8 t cells. however,it is now increasingly recognized that prior infection history impacts on the host immune response. additionally,the order in which these infections are acquired could have a major effect. exploiting the ability to generate large sustained effector memory (i.e. inflationary) t cell populations from murine cytomegalovirus (mcmv) and human adenovirus-subtype (adhu5) 5-beta-galactosidase (ad-lacz) vector,the impact of new infections on pre-existing memory and the capacity of the host’s memory compartment to accommodate multiple inflationary populations from unrelated pathogens was investigated in a murine model. simultaneous and sequential infections,first with mcmv followed by ad-lacz,generated inflationary populations towards both viruses with similar kinetics and magnitude to mono-infected groups. however,in ad-lacz immune mice,subsequent acute mcmv infection led to a rapid decline of the pre-existing ad-lacz-specific inflating population,associated with bystander activation of fas-dependent apoptotic pathways. however,responses were maintained long-term and boosting with ad-lacz led to rapid re-expansion of the inflating population. these data indicate firstly that multiple specificities of inflating memory cells can be acquired at different times and stably co-exist. some acute infections may also deplete pre-existing memory populations,thus revealing the importance of the order of infection acquisition. importantly,immunization with an adhu5 vector did not alter the size of the pre-existing memory. these phenomena are relevant to the development of adenoviral vectors as novel vaccination strategies for diverse infections and cancers. (241 words). © 2017 lee et al.