Abstract
Immunosenescence is believed to be responsible for poor vaccine efficacy in the elderly. To overcome this difficulty, research into vaccination strategies and the mechanisms of immune responses to vaccination is required. By analyzing the innate and adaptive immune responses to vaccination with vaccinia virus (VACV) in mice of different age groups, we found that immune cell recruitment, production of cytokines/chemokines and control of viral replication at the site of intradermal vaccination were preserved in aged mice and were comparable with younger groups. Analysis of cervical draining lymph nodes (dLN) collected after vaccination showed that numbers of germinal center B cells and follicular T helper cells were similar across different age groups. The number of VACV-specific CD8 T cells in the spleen and the levels of serum neutralizing antibodies 1 month after vaccination were also comparable across all age groups. However, following intranasal challenge of vaccinated mice, body weight loss was lower and virus was cleared more rapidly in aged mice than in younger animals. In conclusion, vaccination with VACV can induce an effective immune response and stronger protection in elderly animals. Thus, the development of recombinant VACV-based vaccines against different infectious diseases should be considered as a strategy for improving vaccine immunogenicity and efficacy in the elderly.
Highlights
Old people have increased susceptibility to viral and bacterial infections [1] and in people above 65, about a third of mortality is related to infections [2, 3]
Fifty-four-wo animals were chosen to represent the elderly group based on their general appearance and the death rate in the colony (∼10% lethality over a 6-week period not associated with the experiment)
We show that i.d. vaccination with vaccinia virus (VACV) leads to successful development of immunological memory in old mice bearing an immunosenescent phenotype
Summary
Old people have increased susceptibility to viral and bacterial infections [1] and in people above 65, about a third of mortality is related to infections [2, 3]. The elderly respond poorly to the majority of existing vaccines, including vaccines against influenza virus, pneumococcus, hepatitis B, tetanus, pertussis, and diphtheria [5,6,7,8,9,10]. The reported decline in the immune system fitness with age, is thought to contribute to reduced vaccine efficacy in humans and mice [5, 6, 11, 12]. This decline impacts both innate and adaptive immunity. Dysfunctionality of innate immune cells such as neutrophils, NK cells, monocytes, macrophages and dendritic cells in their ability to migrate, perform phagocytosis, kill bacteria and secrete cytokines have been noted [2, 14,15,16]
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