Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic

Jonah B. Sacha, In Jeong Kim, Lianchun Chen, Jakir H. Ullah, David A. Goodwin, Heather A. Simmons, Daniel I. Schenkman, Frederike Von Pelchrzim, Robert J. Gifford, Francesca A. Nimityongskul, Laura P. Newman, Samantha Wildeboer, Patrick B. Lappin, Daisy Hammond, Philip Castrovinci, Shari M. Piaskowski, Jason S. Reed, Kerry A. Beheler, Tharsika Tharmanathan, Ningli ZhangSophie Muscat-King, Melanie Rieger, Carla Fernandes, Klaus Rumpel, Joseph P. Gardner, Douglas H. Gebhard, Juliann Janies, Ahmed Shoieb, Brian G. Pierce, Dusko Trajkovic, Eva Rakasz, Sing Rong, Michael McCluskie, Clare Christy, James R. Merson, R. Brad Jones, Douglas F. Nixon, Mario A. Ostrowski, Peter T. Loudon, Ingrid M. Pruimboom-Brees, Neil C. Sheppard

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1467-1479
Number of pages13
JournalJournal of Immunology
Volume189
Issue number3
DOIs
StatePublished - Aug 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic'. Together they form a unique fingerprint.

  • Cite this

    Sacha, J. B., Kim, I. J., Chen, L., Ullah, J. H., Goodwin, D. A., Simmons, H. A., Schenkman, D. I., Von Pelchrzim, F., Gifford, R. J., Nimityongskul, F. A., Newman, L. P., Wildeboer, S., Lappin, P. B., Hammond, D., Castrovinci, P., Piaskowski, S. M., Reed, J. S., Beheler, K. A., Tharmanathan, T., ... Sheppard, N. C. (2012). Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic. Journal of Immunology, 189(3), 1467-1479. https://doi.org/10.4049/jimmunol.1200079