title: Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults.
abstract: Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing Ab titers, is increased in the elderly compared with young adults. The T follicular helper cell (Tfh) subset of CD4 T cells provides B cell help in germinal centers and is necessary for class-switched Ab responses. Previous studies suggested a role for circulating Tfh cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults in whom weak vaccine responses are often observed. In this study, we studied cTfh expressing CXCR5 and programmed death-1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and had greater expression of ICOS compared with young adults. At 7 d after inactivated influenza vaccination, cTfh correlated with influenza vaccine-specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh that correlated with reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging.
authors.affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Ramin Sedaghat
authors.initials: RS
authors.lastname: Herati
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Reuter
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Janssen Research & Development, Spring House, PA 19477;
authors.forename: Douglas V
authors.initials: DV
authors.lastname: Dolfi
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Janssen Research & Development, Spring House, PA 19477;
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Mansfield
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106; Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106;
authors.forename: Htin
authors.initials: H
authors.lastname: Aung
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106; Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106;
authors.forename: Osama Z
authors.initials: OZ
authors.lastname: Badwan
authors.affiliation: Wistar Institute, Philadelphia, PA 19104;
authors.forename: Raj K
authors.initials: RK
authors.lastname: Kurupati
authors.affiliation: Wistar Institute, Philadelphia, PA 19104;
authors.forename: Senthil
authors.initials: S
authors.lastname: Kannan
authors.affiliation: Wistar Institute, Philadelphia, PA 19104;
authors.forename: Hildegund
authors.initials: H
authors.lastname: Ertl
authors.affiliation: Division of Geriatrics, Department of Medicine, Duke University Medical Center, Durham, NC 27710; and Geriatric Research, Education, and Clinical Center, Durham VA Medical Center, Durham, NC 27705.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Schmader
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.affiliation: Division of Infectious Disease, Case Western Reserve University, Cleveland, OH 44106; Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106;
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.affiliation: Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; wherry@mail.med.upenn.edu.
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5
chemical_list: D000914:Antibodies, Viral; C095085:CXCR5 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5