Immunogenicity and efficacy of a DNA vaccine in aged mice.
The immunogenicity and protective efficacy of a DNA vaccine encoding the circumsporozoite protein of the Plasmodium yoelii malaria parasite was evaluated in young (2 months) versus aged (>26 months) BALB/c mice. The primary and secondary humoral immune response of aged mice was 19- and 7-fold lower, respectively, than that of similarly treated young animals (p < .01). Cytotoxic T lymphocyte activity in aged mice was also lower than in younger animals. The vaccine response of aged animals was characterized by a 6-fold increase in interleukin-4 and a 3-fold increase in interferon-gamma (IFN-gamma) secreting cells, whereas in young animals immunization only stimulated the production of the type 1 cytokine IFN-gamma. Overall, 80% of young vaccinated mice were protected from subsequent challenge with live malaria sporozoites whereas only 40% of aged mice were protected. These results are the first to demonstrate that DNA vaccination induces less effective immunity in aged than young animals.
Klinman
D M
DM
Section of Retroviral Immunology, Division of Viral Products, fCenter for Biologics Evaluation and Research, Food and Drug Administration, Bethesda 20892, USA. klinman@a1.cber.fda.gov
Conover
J
J
Bloom
E T
ET
Weiss
W
W
D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan