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

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleVaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic.
Publication TypeJournal Article
Year of Publication2012
AuthorsSacha, JB, Kim, I-J, Chen, L, Ullah, JH, Goodwin, DA, Simmons, HA, Schenkman, DI, von Pelchrzim, F, Gifford, RJ, Nimityongskul, FA, Newman, LP, Wildeboer, S, Lappin, PB, Hammond, D, Castrovinci, P, Piaskowski, SM, Reed, JS, Beheler, KA, Tharmanathan, T, Zhang, N, Muscat-King, S, Rieger, M, Fernandes, C, Rumpel, K, Gardner, JP, Gebhard, DH, Janies, J, Shoieb, A, Pierce, BG, Trajkovic, D, Rakasz, E, Rong, S, McCluskie, M, Christy, C, Merson, JR, R Jones, B, Nixon, DF, Ostrowski, MA, Loudon, PT, Pruimboom-Brees, IM, Sheppard, NC
JournalJ Immunol
Volume189
Issue3
Pagination1467-79
Date Published2012 Aug 1
ISSN1550-6606
KeywordsAdult, AIDS Vaccines, Amino Acid Sequence, Animals, Cancer Vaccines, Disease Models, Animal, DNA Transposable Elements, Endogenous Retroviruses, env Gene Products, Human Immunodeficiency Virus, Female, gag Gene Products, Human Immunodeficiency Virus, Humans, Macaca mulatta, Male, Mice, Mice, Inbred BALB C, Molecular Sequence Data
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.

DOI10.4049/jimmunol.1200079
Alternate JournalJ. Immunol.
PubMed ID22745376
PubMed Central IDPMC3401319
Grant ListP51 OD011106 / OD / NIH HHS / United States
R01 AI076059 / AI / NIAID NIH HHS / United States
R21 AI087474 / AI / NIAID NIH HHS / United States
R21 AI087474 / AI / NIAID NIH HHS / United States