Comparative Analysis of Simian Immunodeficiency Virus Gag-Specific Effector and Memory CD8+ T Cells Induced by Different Adenovirus Vectors

• Type of Material: Article
• Authors: Wendy G. Tan, Emory University; Hyun-Tak Jin, Emory University; Erin E. West, Emory University; Pablo Penaloza-MacMaster, Beth Israel Deaconess Medical Center; Andreas Wieland, Emory University; Michael J. Zilliox, Emory University; M. Juliana McElrath, Fred Hutchinson Cancer Research Institute; Dan H. Barouch, Beth Israel Deaconess Medical Center; Rafi Ahmed, Emory University
• Language: English
• Date: 2013-02
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2013, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://jvi.asm.org/content/87/3/1359
• Title of Journal or Parent Work: Journal of Virology
• Volume: 87
• Issue: 3
• Start Page: 1359
• End Page: 1372
• Grant/Funding Information: This work was supported by grants from the Bill and Melinda Gates Foundation (38645 to M.J.M. and R.A. and 1033091 and 1040741 to D.H.B.) and the National Institutes of Health (AI30048 to R.A.; AI007245 to P.P.M.; AI060354, AI066924, AI078526, and AI096040 to D.H.B.; and NIAID award UM1AI100663 to R.A.).
• Research Categories: Health Sciences, Immunology; Biology, Virology; Biology, Microbiology

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.