title: Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic.
abstract: The expression of endogenous retrotransposable elements, including long interspersed nuclear element 1 (LINE-1 or L1) and human endogenous retrovirus, accompanies neoplastic transformation and infection with viruses such as HIV. The ability to engender immunity safely against such self-antigens would facilitate the development of novel vaccines and immunotherapies. In this article, we address the safety and immunogenicity of vaccination with these elements. We used immunohistochemical analysis and literature precedent to identify potential off-target tissues in humans and establish their translatability in preclinical species to guide safety assessments. Immunization of mice with murine L1 open reading frame 2 induced strong CD8 T cell responses without detectable tissue damage. Similarly, immunization of rhesus macaques with human LINE-1 open reading frame 2 (96% identity with macaque), as well as simian endogenous retrovirus-K Gag and Env, induced polyfunctional T cell responses to all Ags, and Ab responses to simian endogenous retrovirus-K Env. There were no adverse safety or pathological findings related to vaccination. These studies provide the first evidence, to our knowledge, that immune responses can be induced safely against this class of self-antigens and pave the way for investigation of them as HIV- or tumor-associated targets.
authors: AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53705, USA.
authors: Jonah B
authors: JB
authors: Sacha
authors: In-Jeong
authors: IJ
authors: Kim
authors: Lianchun
authors: L
authors: Chen
authors: Jakir H
authors: JH
authors: Ullah
authors: David A
authors: DA
authors: Goodwin
authors: Heather A
authors: HA
authors: Simmons
authors: Daniel I
authors: DI
authors: Schenkman
authors: Frederike
authors: F
authors: von Pelchrzim
authors: Robert J
authors: RJ
authors: Gifford
authors: Francesca A
authors: FA
authors: Nimityongskul
authors: Laura P
authors: LP
authors: Newman
authors: Samantha
authors: S
authors: Wildeboer
authors: Patrick B
authors: PB
authors: Lappin
authors: Daisy
authors: D
authors: Hammond
authors: Philip
authors: P
authors: Castrovinci
authors: Shari M
authors: SM
authors: Piaskowski
authors: Jason S
authors: JS
authors: Reed
authors: Kerry A
authors: KA
authors: Beheler
authors: Tharsika
authors: T
authors: Tharmanathan
authors: Ningli
authors: N
authors: Zhang
authors: Sophie
authors: S
authors: Muscat-King
authors: Melanie
authors: M
authors: Rieger
authors: Carla
authors: C
authors: Fernandes
authors: Klaus
authors: K
authors: Rumpel
authors: Joseph P
authors: JP
authors: Gardner
authors: Douglas H
authors: DH
authors: Gebhard
authors: Juliann
authors: J
authors: Janies
authors: Ahmed
authors: A
authors: Shoieb
authors: Brian G
authors: BG
authors: Pierce
authors: Dusko
authors: D
authors: Trajkovic
authors: Eva
authors: E
authors: Rakasz
authors: Sing
authors: S
authors: Rong
authors: Michael
authors: M
authors: McCluskie
authors: Clare
authors: C
authors: Christy
authors: James R
authors: JR
authors: Merson
authors: R Brad
authors: RB
authors: Jones
authors: Douglas F
authors: DF
authors: Nixon
authors: Mario A
authors: MA
authors: Ostrowski
authors: Peter T
authors: PT
authors: Loudon
authors: Ingrid M
authors: IM
authors: Pruimboom-Brees
authors: Neil C
authors: NC
authors: Sheppard
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D004251:DNA Transposable Elements / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D019496:Cancer Vaccines; D004251:DNA Transposable Elements; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus