Comparative analysis of simian immunodeficiency virus gag-specific effector and memory CD8+ T cells induced by different adenovirus vectors Journal Article

Local Library Link: Find It @ Loyola

Authors: Tan, W. G.; Jin, H. T.; West, E. E.; Penaloza-MacMaster, P.; Wieland, A.; Zilliox, M. J.; McElrath, M. J.; Barouch, D. H.; Ahmed, R.
Article Title: Comparative analysis of simian immunodeficiency virus gag-specific effector and memory CD8+ T cells induced by different adenovirus vectors
Abstract: Adenovirus (Ad) vectors are widely used as experimental vaccines against several infectious diseases, but the magnitude, phenotype, and functionality of CD8(+) T cell responses induced by different adenovirus serotypes have not been compared. To address this question, we have analyzed simian immunodeficiency virus Gag-specific CD8(+) T cell responses in mice following vaccination with Ad5, Ad26, and Ad35. Our results show that although Ad5 is more immunogenic than Ad26 and Ad35, the phenotype, function, and recall potential of memory CD8(+) T cells elicited by these vectors are substantially different. Ad26 and Ad35 vectors generated CD8(+) T cells that display the phenotype and function of long-lived memory T cells, whereas Ad5 vector-elicited CD8(+) T cells are of a more terminally differentiated phenotype. In addition, hepatic memory CD8(+) T cells elicited by Ad26 and Ad35 mounted more robust recall proliferation following secondary challenge than those induced by Ad5. Furthermore, the boosting potential was higher following priming with alternative-serotype Ad vectors than with Ad5 vectors in heterologous prime-boost regimens. Anamnestic CD8(+) T cell responses were further enhanced when the duration between priming and boosting was extended from 30 to 60 days. Our results demonstrate that heterologous prime-boost vaccine regimens with alternative-serotype Ad vectors elicited more functional memory CD8(+) T cells than any of the regimens containing Ad5. In summary, these results suggest that alternative-serotype Ad vectors will prove useful as candidates for vaccine development against human immunodeficiency virus type 1 and other pathogens and also emphasize the importance of a longer rest period between prime and boost for generating optimal CD8(+) T cell immunity.
Journal Title: Journal of virology
Volume: 87
Issue: 3
ISSN: 1098-5514; 0022-538X
Publisher: American Society for Microbiology. All Rights Reserved  
Journal Place: United States
Date Published: 2013
Start Page: 1359
End Page: 1372
Language: eng
DOI/URL:

10.1128/JVI.02055-12

10.1128/JVI.02055-12
Notes: LR: 20130718; GR: AI007245/AI/NIAID NIH HHS/United States; GR: AI060354/AI/NIAID NIH HHS/United States; GR: AI066924/AI/NIAID NIH HHS/United States; GR: AI078526/AI/NIAID NIH HHS/United States; GR: AI096040/AI/NIAID NIH HHS/United States; GR: AI30048/AI/NIAID NIH HHS/United States; GR: P30 AI060354/AI/NIAID NIH HHS/United States; GR: R01 AI066924/AI/NIAID NIH HHS/United States; GR: R01 AI091493/AI/NIAID NIH HHS/United States; GR: U19 AI078526/AI/NIAID NIH HHS/United States; GR: U19 AI096040/AI/NIAID NIH HHS/United States; GR: UM1 AI100663/AI/NIAID NIH HHS/United States; GR: UM1AI100663/AI/NIAID NIH HHS/United States; JID: 0113724; 0 (Gene Products, gag); 0 (SAIDS Vaccines); OID: NLM: PMC3554140; 2012/11/21 [aheadofprint]; ppublish