학술논문

Efficacy of Influenza Vaccination of Elderly Rhesus Macaques Is Dramatically Improved by Addition of a Cationic Lipid/DNA Adjuvant
Document Type
article
Source
The Journal of Infectious Diseases. 209(1)
Subject
Biodefense
Genetics
Prevention
Emerging Infectious Diseases
Pneumonia & Influenza
Influenza
Vaccine Related
Infectious Diseases
Aging
Immunization
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
3.4 Vaccines
Prevention of disease and conditions
and promotion of well-being
Infection
Animals
Antibodies
Viral
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Female
Influenza Vaccines
Integrin alpha4
Integrin beta Chains
Interferon-gamma
Macaca mulatta
Male
Nasal Lavage Fluid
Orthomyxoviridae Infections
Vaccines
Inactivated
inactivated vaccine
elderly
macaques
immunosenescence
mucosal
antibody Liters
CDS plus T cells
CD8+ T cells
antibody titers
Biological Sciences
Medical and Health Sciences
Microbiology
Language
Abstract
BackgroundThe 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.MethodsElderly (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).ResultsWe 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.ConclusionsThese results demonstrate that CLDC can enhance the immunogenicity and efficacy of a licensed TIV in immunosenescent elderly monkeys.