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

• DOI: 10.1371/journal.ppat.1006782
• Publication Date: 2017-12-27T19:15:11Z
• Authors: Lian N. Lee; Beatrice Bolinger; Zoltan Banki; Catherine de Lara; Andrew J. Highton; Julia M. Colston; Claire Hutchings; Paul Klenerman
• Keywords: Bystander effect; Memory T cell

The efficacies of many new T cell vaccines rely on generating large populations long-lived pathogen-specific effector memory CD8 cells. However, it is now increasingly recognized that prior infection history impacts the host immune response. Additionally, order in which these infections are acquired could have a major effect. Exploiting ability to generate sustained (i.e. inflationary) from murine cytomegalovirus (MCMV) and human Adenovirus-subtype (AdHu5) 5-beta-galactosidase (Ad-lacZ) vector, impact pre-existing capacity host's compartment accommodate multiple inflationary unrelated pathogens was investigated model. Simultaneous sequential infections, first with MCMV followed by Ad-lacZ, generated towards both viruses similar kinetics magnitude mono-infected groups. Ad-lacZ mice, subsequent acute led rapid decline Ad-LacZ-specific inflating population, associated bystander activation Fas-dependent apoptotic pathways. responses were maintained long-term boosting re-expansion population. These data indicate firstly specificities cells can be at different times stably co-exist. Some may also deplete populations, thus revealing importance acquisition. Importantly, immunization an AdHu5 vector did not alter size memory. phenomena relevant development adenoviral vectors as novel vaccination strategies for diverse cancers. (241 words)