title: Efficacy of influenza vaccination of elderly rhesus macaques is dramatically improved by addition of a cationic lipid/DNA adjuvant.
abstract: BACKGROUND
  The decreased immune response among elderly individuals results in reduced influenza vaccine efficacy. Strategies to improve vaccine efficacy in elderly individuals are needed. The goal of this study was to determine whether a cationic lipid/DNA complex (CLDC) can improve the efficacy of the trivalent inactivated influenza vaccine Fluzone in elderly nonhuman primates.
  
  
  METHODS
  Elderly (age, >18 years) rhesus macaques were vaccinated 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 naive CD4(+) T cells, naive CD8(+) T cells, and B cells as compared to juvenile monkeys. Furthermore, on the day of challenge, recipients of Fluzone/CLDC had significantly higher plasma anti-influenza virus immunoglobulin G (P < .001) and immunoglobulin A (P < .001) titers than recipients of Fluzone alone. After virus challenge, only the Fluzone/CLDC-vaccinated animals had a significantly lower level of virus replication (P < .01) relative to the unvaccinated control animals.
  
  
  CONCLUSIONS
  These results demonstrate that CLDC can enhance the immunogenicity and efficacy of a licensed TIV in immunosenescent elderly monkeys.
authors.affiliation: Center for Comparative Medicine.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Carroll
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Matzinger
authors.forename: Peter A
authors.initials: PA
authors.lastname: Barry
authors.forename: Michael B
authors.initials: MB
authors.lastname: McChesney
authors.forename: Jeffery
authors.initials: J
authors.lastname: Fairman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D039441:Integrin alpha4 / Q000097:blood; D039641:Integrin beta Chains / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D017817:Nasal Lavage Fluid / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D039641:Integrin beta Chains; D015164:Vaccines, Inactivated; C091368:integrin beta7; D039441:Integrin alpha4; D007371:Interferon-gamma
keywords: CD8+ T cells; antibody titers; elderly; immunosenescence; inactivated vaccine; macaques; mucosal