1. Vaccination with Cancer- and HIV Infection-Associated Endogenous Retrotransposable Elements Is Safe and Immunogenic
- Author
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James R. Merson, Lianchun Chen, In-Jeong Kim, Daisy Hammond, Clare Christy, Tharsika Tharmanathan, R. Brad Jones, Heather A. Simmons, Mario A. Ostrowski, Kerry A Beheler, Eva G. Rakasz, Jakir Hussain Ullah, Neil C. Sheppard, Carla Fernandes, Dusko Trajkovic, Peter T. Loudon, Douglas F. Nixon, Jonah B. Sacha, Philip A. Castrovinci, Jason S. Reed, Melanie Rieger, Patrick B. Lappin, Ingrid M. Pruimboom-Brees, Daniel Schenkman, Juliann Janies, Ningli Zhang, Joseph P. Gardner, Sing Rong, Douglas H Gebhard, Ahmed M. Shoieb, Michael J. McCluskie, Shari M. Piaskowski, Klaus Rumpel, Laura Newman, Francesca A. Nimityongskul, Robert J Gifford, Brian G. Pierce, Frederike von Pelchrzim, David A. Goodwin, Sophie Muscat-King, and Samantha E. Wildeboer
- Subjects
Adult ,Male ,T cell ,Molecular Sequence Data ,Immunology ,Endogenous retrovirus ,Biology ,Cancer Vaccines ,gag Gene Products, Human Immunodeficiency Virus ,Article ,Mice ,Immune system ,Immunity ,medicine ,Animals ,Humans ,Immunology and Allergy ,Neoplastic transformation ,Amino Acid Sequence ,AIDS Vaccines ,Mice, Inbred BALB C ,Immunogenicity ,Endogenous Retroviruses ,env Gene Products, Human Immunodeficiency Virus ,Macaca mulatta ,Virology ,Vaccination ,Disease Models, Animal ,medicine.anatomical_structure ,Immunization ,DNA Transposable Elements ,Female - 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.
- Published
- 2012