tetano
Editor, Senior Moderator
J Infect Dis. (2013) doi: 10.1093/infdis/jit540 First published online: October 17, 2013
The effectiveness of influenza vaccination of elderly rhesus macaques is dramatically improved by addition of a cationic lipid/DNA adjuvant
Timothy D. Carroll1,2,
Shannon R. Matzinger1,2,
Peter A. Barry1,2,3,
Michael B. McChesney2,3,
Jeffery Fairman4 and
Christopher J. Miller1,2,5,*
+ Author Affiliations
1Center for Comparative Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
2California National Primate Research Center, University of California, Davis, One Shields Ave, Davis, California 95616, USA
3Department of Pathology and Laboratory Medicine. School of Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
4Colby Pharmaceutical Company, San Jose, California 95138, USA
5Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
↵*Correspondence to: Christopher J. Miller, CNPRC, UC Davis, One Shields Ave. Davis, CA 95616, Phone: (530) 752-0447, Fax: (530) 754-4411, Email: cjmiller@ucdavis.edu
Abstract
Background. The decline in immunity in the elderly results in reduced influenza vaccine efficacy. Strategies to improve vaccine efficacy in the elderly are needed. The goal of this study was to determine if the adjuvant activity of a cationic lipid/DNA complex (CLDC) can improve the efficacy of the inactivated influenza vaccine Fluzone? in elderly non-human primates.
Methods. Elderly (>18 years old) rhesus macaques were immunized with Fluzone? with or without CLDC and challenged with a human seasonal influenza virus isolate, A/Memphis/7/2001 (H1N1).
Results. We found that elderly macaques have significantly lower levels of circulating na?ve CD4+ T cells, na?ve CD8+ T cells and B cells compared to juvenile monkeys. Further, on the day of challenge, Fluzone/CLDC immunized animals had significantly higher plasma anti-influenza IgG (p<0.001) and IgA (p<0.001) titers than the un-adjuvanted immunized monkeys. After virus challenge, only the Fluzone/CLDC immunized animals had a significantly lower level of virus replication (p<0.01) relative to the unimmunized control animals.
Conclusions. These results demonstrate that the CLDC adjuvant can enhance the immunogenicity and efficacy of a licensed inactivated influenza vaccine in immunosenescent elderly monkeys.
http://jid.oxfordjournals.org/content/early/2013/10/17/infdis.jit540.abstract
The effectiveness of influenza vaccination of elderly rhesus macaques is dramatically improved by addition of a cationic lipid/DNA adjuvant
Timothy D. Carroll1,2,
Shannon R. Matzinger1,2,
Peter A. Barry1,2,3,
Michael B. McChesney2,3,
Jeffery Fairman4 and
Christopher J. Miller1,2,5,*
+ Author Affiliations
1Center for Comparative Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
2California National Primate Research Center, University of California, Davis, One Shields Ave, Davis, California 95616, USA
3Department of Pathology and Laboratory Medicine. School of Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
4Colby Pharmaceutical Company, San Jose, California 95138, USA
5Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, One Shields Ave, Davis, California 95616, USA
↵*Correspondence to: Christopher J. Miller, CNPRC, UC Davis, One Shields Ave. Davis, CA 95616, Phone: (530) 752-0447, Fax: (530) 754-4411, Email: cjmiller@ucdavis.edu
Abstract
Background. The decline in immunity in the elderly results in reduced influenza vaccine efficacy. Strategies to improve vaccine efficacy in the elderly are needed. The goal of this study was to determine if the adjuvant activity of a cationic lipid/DNA complex (CLDC) can improve the efficacy of the inactivated influenza vaccine Fluzone? in elderly non-human primates.
Methods. Elderly (>18 years old) rhesus macaques were immunized with Fluzone? with or without CLDC and challenged with a human seasonal influenza virus isolate, A/Memphis/7/2001 (H1N1).
Results. We found that elderly macaques have significantly lower levels of circulating na?ve CD4+ T cells, na?ve CD8+ T cells and B cells compared to juvenile monkeys. Further, on the day of challenge, Fluzone/CLDC immunized animals had significantly higher plasma anti-influenza IgG (p<0.001) and IgA (p<0.001) titers than the un-adjuvanted immunized monkeys. After virus challenge, only the Fluzone/CLDC immunized animals had a significantly lower level of virus replication (p<0.01) relative to the unimmunized control animals.
Conclusions. These results demonstrate that the CLDC adjuvant can enhance the immunogenicity and efficacy of a licensed inactivated influenza vaccine in immunosenescent elderly monkeys.
http://jid.oxfordjournals.org/content/early/2013/10/17/infdis.jit540.abstract