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J Clin Invest. doi:10.1172/JCI57834.
Copyright ? 2011, The American Society for Clinical Investigation.
Research Article
Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Sanae Sasaki1,2, Meghan Sullivan3,4, Carlos F. Narvaez1,2, Tyson H. Holmes5, David Furman1, Nai-Ying Zheng3, Madhuri Nishtala3, Jens Wrammert6,7, Kenneth Smith8, Judith A. James8, Cornelia L. Dekker9, Mark M. Davis1, Patrick C. Wilson3, Harry B. Greenberg1,2,10 and Xiao-Song He2,10
1Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, California, USA.
2VA Palo Alto Health Care System, Palo Alto, California, USA.
3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.
4Committee on Molecular Medicine and Molecular Pathology, University of Chicago, Chicago, Illinois, USA.
5Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
6Emory Vaccine Center and
7Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.
8Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
9Department of Pediatrics and
10Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Address correspondence to: Patrick C. Wilson, University of Chicago, BSLC/Jules F. Knapp Bldg., 924 E. 57th Street, R414, Chicago, Illinois 60637, USA. Phone: 773.702.9009; Fax: 773.702.1576; E-mail: wilsonp@uchicago.edu. Or to: Xiao-Song He, VA Medical Center 154C, 3801 Miranda Ave., Palo Alto, California 94304, USA. Phone: 650.493.5000, ext. 66135; Fax: 650.852.3259; E-mail: xiaosong@stanford.edu.
Authorship note: Sanae Sasaki and Meghan Sullivan contributed equally to this work.
Published July 25, 2011
Received for publication March 3, 2011, and accepted in revised form June 15, 2011.
During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.
Copyright ? 2011, The American Society for Clinical Investigation.
Research Article
Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Sanae Sasaki1,2, Meghan Sullivan3,4, Carlos F. Narvaez1,2, Tyson H. Holmes5, David Furman1, Nai-Ying Zheng3, Madhuri Nishtala3, Jens Wrammert6,7, Kenneth Smith8, Judith A. James8, Cornelia L. Dekker9, Mark M. Davis1, Patrick C. Wilson3, Harry B. Greenberg1,2,10 and Xiao-Song He2,10
1Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, California, USA.
2VA Palo Alto Health Care System, Palo Alto, California, USA.
3Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.
4Committee on Molecular Medicine and Molecular Pathology, University of Chicago, Chicago, Illinois, USA.
5Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
6Emory Vaccine Center and
7Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, Georgia, USA.
8Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
9Department of Pediatrics and
10Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
Address correspondence to: Patrick C. Wilson, University of Chicago, BSLC/Jules F. Knapp Bldg., 924 E. 57th Street, R414, Chicago, Illinois 60637, USA. Phone: 773.702.9009; Fax: 773.702.1576; E-mail: wilsonp@uchicago.edu. Or to: Xiao-Song He, VA Medical Center 154C, 3801 Miranda Ave., Palo Alto, California 94304, USA. Phone: 650.493.5000, ext. 66135; Fax: 650.852.3259; E-mail: xiaosong@stanford.edu.
Authorship note: Sanae Sasaki and Meghan Sullivan contributed equally to this work.
Published July 25, 2011
Received for publication March 3, 2011, and accepted in revised form June 15, 2011.
During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.
