Unknown

Dataset Information

0

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


ABSTRACT: 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).

SUBMITTER: Lee LN 

PROVIDER: S-EPMC5760110 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Lee Lian N LN   Bolinger Beatrice B   Banki Zoltan Z   de Lara Catherine C   Highton Andrew J AJ   Colston Julia M JM   Hutchings Claire C   Klenerman Paul P  

PLoS pathogens 20171227 12


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 Adenoviru  ...[more]

Similar Datasets

| S-EPMC3672979 | biostudies-literature
| S-EPMC6219444 | biostudies-other
| S-EPMC3188546 | biostudies-other
| S-EPMC5117776 | biostudies-literature
| S-EPMC7563500 | biostudies-literature
| S-EPMC3203160 | biostudies-literature
| S-EPMC6688724 | biostudies-literature
| S-EPMC4081724 | biostudies-literature
2019-03-12 | GSE128147 | GEO
| S-EPMC3655265 | biostudies-literature