Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

M. A. Kutzler, K. A. Kraynyak, S. J. Nagle, Rose Parkinson, D. Zharikova, Michael Anand Chattergoon, H. Maguire, K. Muthumani, K. Ugen, D. B. Weiner

Research output: Contribution to journalArticle

Abstract

A hurdle facing DNA vaccine development is the ability to generate strong immune responses systemically and at local immune sites. We report a novel systemically administered DNA vaccination strategy using intramuscular codelivery of CCL27 or CCL28, which elicited elevated peripheral IFN-γ and antigen-specific IgG while driving antigen-specific T-cell secretion of cytokine and antibody production in the gut-associated lymphoid tissue and lung. This strategy resulted in induction of long-lived antibody responses that neutralized influenza A/PR8/34 and protected mice from morbidity and mortality associated with a lethal intranasal viral challenge. This is the first example of the use of CCL27 and CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting further examination of this approach for manipulation of vaccine-induced immunity impacting both quality and phenotype of responses.

Original languageEnglish (US)
Pages (from-to)72-82
Number of pages11
JournalGene Therapy
Volume17
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Chemokine CCL27
DNA Vaccines
Antibody Formation
Immunity
Plasmids
Antigens
Lymphoid Tissue
Human Influenza
Vaccination
Vaccines
Immunoglobulin G
Cytokines
Morbidity
T-Lymphocytes
Phenotype
Lung
Mortality
DNA

Keywords

  • DNA vaccines
  • Immune modulation
  • Immune responses
  • Molecular adjuvants

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo. / Kutzler, M. A.; Kraynyak, K. A.; Nagle, S. J.; Parkinson, Rose; Zharikova, D.; Chattergoon, Michael Anand; Maguire, H.; Muthumani, K.; Ugen, K.; Weiner, D. B.

In: Gene Therapy, Vol. 17, No. 1, 01.2010, p. 72-82.

Research output: Contribution to journalArticle

Kutzler, MA, Kraynyak, KA, Nagle, SJ, Parkinson, R, Zharikova, D, Chattergoon, MA, Maguire, H, Muthumani, K, Ugen, K & Weiner, DB 2010, 'Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo', Gene Therapy, vol. 17, no. 1, pp. 72-82. https://doi.org/10.1038/gt.2009.112
Kutzler, M. A. ; Kraynyak, K. A. ; Nagle, S. J. ; Parkinson, Rose ; Zharikova, D. ; Chattergoon, Michael Anand ; Maguire, H. ; Muthumani, K. ; Ugen, K. ; Weiner, D. B. / Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo. In: Gene Therapy. 2010 ; Vol. 17, No. 1. pp. 72-82.
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