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

Jonah 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

25 Citations (Scopus)

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

Fingerprint

Endogenous Retroviruses
Simian Retroviruses
HIV Infections
Vaccination
Autoantigens
Safety
Open Reading Frames
Immunization
Long Interspersed Nucleotide Elements
HIV
T-Lymphocytes
Neoplasms
Macaca
Virus Diseases
Macaca mulatta
Immunotherapy
Immunity
Vaccines

ASJC Scopus subject areas

  • Immunology

Cite this

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

In: Journal of Immunology, Vol. 189, No. 3, 01.08.2012, p. 1467-1479.

Research output: Contribution to journalArticle

Sacha, J, Kim, IJ, 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, Jones, RB, Nixon, DF, Ostrowski, MA, Loudon, PT, Pruimboom-Brees, IM & Sheppard, NC 2012, 'Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic', Journal of Immunology, vol. 189, no. 3, pp. 1467-1479. https://doi.org/10.4049/jimmunol.1200079
Sacha, Jonah ; Kim, In Jeong ; Chen, Lianchun ; Ullah, Jakir H. ; Goodwin, David A. ; Simmons, Heather A. ; Schenkman, Daniel I. ; Von Pelchrzim, Frederike ; Gifford, Robert J. ; Nimityongskul, Francesca A. ; Newman, Laura P. ; Wildeboer, Samantha ; Lappin, Patrick B. ; Hammond, Daisy ; Castrovinci, Philip ; Piaskowski, Shari M. ; Reed, Jason S. ; Beheler, Kerry A. ; Tharmanathan, Tharsika ; Zhang, Ningli ; Muscat-King, Sophie ; Rieger, Melanie ; Fernandes, Carla ; Rumpel, Klaus ; Gardner, Joseph P. ; Gebhard, Douglas H. ; Janies, Juliann ; Shoieb, Ahmed ; Pierce, Brian G. ; Trajkovic, Dusko ; Rakasz, Eva ; Rong, Sing ; McCluskie, Michael ; Christy, Clare ; Merson, James R. ; Jones, R. Brad ; Nixon, Douglas F. ; Ostrowski, Mario A. ; Loudon, Peter T. ; Pruimboom-Brees, Ingrid M. ; Sheppard, Neil C. / Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic. In: Journal of Immunology. 2012 ; Vol. 189, No. 3. pp. 1467-1479.
@article{08e2f2322a3f4b21afd15e72ec25b0c3,
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.",
author = "Jonah Sacha and Kim, {In Jeong} and Lianchun Chen and Ullah, {Jakir H.} and Goodwin, {David A.} and Simmons, {Heather A.} and Schenkman, {Daniel I.} and {Von Pelchrzim}, Frederike and Gifford, {Robert J.} and Nimityongskul, {Francesca A.} and Newman, {Laura P.} and Samantha Wildeboer and Lappin, {Patrick B.} and Daisy Hammond and Philip Castrovinci and Piaskowski, {Shari M.} and Reed, {Jason S.} and Beheler, {Kerry A.} and Tharsika Tharmanathan and Ningli Zhang and Sophie Muscat-King and Melanie Rieger and Carla Fernandes and Klaus Rumpel and Gardner, {Joseph P.} and Gebhard, {Douglas H.} and Juliann Janies and Ahmed Shoieb and Pierce, {Brian G.} and Dusko Trajkovic and Eva Rakasz and Sing Rong and Michael McCluskie and Clare Christy and Merson, {James R.} and Jones, {R. Brad} and Nixon, {Douglas F.} and Ostrowski, {Mario A.} and Loudon, {Peter T.} and Pruimboom-Brees, {Ingrid M.} and Sheppard, {Neil C.}",
year = "2012",
month = "8",
day = "1",
doi = "10.4049/jimmunol.1200079",
language = "English (US)",
volume = "189",
pages = "1467--1479",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Vaccination with cancer- and HIV infection-associated endogenous retrotransposable elements is safe and immunogenic

AU - Sacha, Jonah

AU - Kim, In Jeong

AU - Chen, Lianchun

AU - Ullah, Jakir H.

AU - Goodwin, David A.

AU - Simmons, Heather A.

AU - Schenkman, Daniel I.

AU - Von Pelchrzim, Frederike

AU - Gifford, Robert J.

AU - Nimityongskul, Francesca A.

AU - Newman, Laura P.

AU - Wildeboer, Samantha

AU - Lappin, Patrick B.

AU - Hammond, Daisy

AU - Castrovinci, Philip

AU - Piaskowski, Shari M.

AU - Reed, Jason S.

AU - Beheler, Kerry A.

AU - Tharmanathan, Tharsika

AU - Zhang, Ningli

AU - Muscat-King, Sophie

AU - Rieger, Melanie

AU - Fernandes, Carla

AU - Rumpel, Klaus

AU - Gardner, Joseph P.

AU - Gebhard, Douglas H.

AU - Janies, Juliann

AU - Shoieb, Ahmed

AU - Pierce, Brian G.

AU - Trajkovic, Dusko

AU - Rakasz, Eva

AU - Rong, Sing

AU - McCluskie, Michael

AU - Christy, Clare

AU - Merson, James R.

AU - Jones, R. Brad

AU - Nixon, Douglas F.

AU - Ostrowski, Mario A.

AU - Loudon, Peter T.

AU - Pruimboom-Brees, Ingrid M.

AU - Sheppard, Neil C.

PY - 2012/8/1

Y1 - 2012/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864123257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864123257&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1200079

DO - 10.4049/jimmunol.1200079

M3 - Article

C2 - 22745376

AN - SCOPUS:84864123257

VL - 189

SP - 1467

EP - 1479

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -