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: 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 Zhang, Sophie Muscat-King, Melanie Rieger, Carla Fernandes, Klaus Rumpel, Joseph P Gardner 2nd, 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
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 189 Issue 3 Pg. 1467-79 (Aug 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22745376 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• AIDS Vaccines
• Cancer Vaccines
• DNA Transposable Elements
• env Gene Products, Human Immunodeficiency Virus
• gag Gene Products, Human Immunodeficiency Virus

Topics

• AIDS Vaccines (administration & dosage, genetics, immunology)
• Adult
• Amino Acid Sequence
• Animals
• Cancer Vaccines (administration & dosage, genetics, immunology)
• DNA Transposable Elements (genetics, immunology)
• Disease Models, Animal
• Endogenous Retroviruses (genetics, immunology, metabolism)
• Female
• Humans
• Macaca mulatta
• Male
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• env Gene Products, Human Immunodeficiency Virus (genetics, immunology)
• gag Gene Products, Human Immunodeficiency Virus (genetics, immunology)