title: Alternative serotype adenovirus vaccine vectors elicit memory T cells with enhanced anamnestic capacity compared to Ad5 vectors.
abstract: The failure of the adenovirus serotype 5 (Ad5) vector-based human immunodeficiency virus type 1 (HIV-1) vaccine in the STEP study has led to the development of adenovirus vectors derived from alternative serotypes, such as Ad26, Ad35, and Ad48. We have recently demonstrated that vaccines using alternative-serotype Ad vectors confer partial protection against stringent simian immunodeficiency virus (SIV) challenges in rhesus monkeys. However, phenotypic differences between the T cell responses elicited by Ad5 and those of alternative-serotype Ad vectors remain unexplored. Here, we report the magnitude, phenotype, functionality, and recall capacity of memory T cell responses elicited in mice by Ad5, Ad26, Ad35, and Ad48 vectors expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP). Our data demonstrate that memory T cells elicited by Ad5 vectors were high in magnitude but exhibited functional exhaustion and decreased anamnestic potential following secondary antigen challenge compared to Ad26, Ad35, and Ad48 vectors. These data suggest that vaccination with alternative-serotype Ad vectors offers substantial immunological advantages over Ad5 vectors, in addition to circumventing high baseline Ad5-specific neutralizing antibody titers.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Penaloza-MacMaster
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Provine
authors.forename: Joshua
authors.initials: J
authors.lastname: Ra
authors.forename: Erica N
authors.initials: EN
authors.lastname: Borducchi
authors.forename: Anna
authors.initials: A
authors.lastname: McNally
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Simmons
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Iampietro
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D016915:AIDS Vaccines