Mousepox in Aged Mice

描述(申请人提供)：众所周知，对病毒感染的抵抗力和接种疫苗后产生保护性免疫的能力随着年龄的增长而下降。虽然我们大多数人都接种了疫苗，可能对许多常见的病毒疾病具有终身免疫力，但我们最近更加意识到，可能会出现新的传染病，可能会发生具有新的已知病毒株的大流行，以及高致病性微生物可能被用作武器。在每一种情况下，没有免疫力的老年人患病和死亡的风险都比年轻人高得多。由于老年人占世界人口的相当大比例，了解原因并努力克服因年龄而丧失对病毒疾病的自然和后天抵抗力的后果，是重大的公共卫生利益。然而，对人类对病毒疾病丧失抵抗力的直接详细分析是不可能的，必须使用适当的动物模型。鼠痘是一种经常致命的小鼠疾病，由正痘病毒(OPV)皮疹病毒(ECTV)引起，这种疾病与人类天花(由OPV天花病毒(VARV)引起)和猴痘(由同音OPV引起)非常相似。一些品系的小鼠，如C57BL/6(B6)，已知对鼠痘具有天然抵抗力。然而，我们最近发现，B6小鼠随着年龄的增长会失去这种抵抗力。因此，比较幼龄和老年B6小鼠对原发ECTV感染的免疫功能，为了解年龄相关的病毒抵抗力丧失提供了一个很好的模型。此外，由于鼠痘可以通过天花疫苗预防，我们的新发现为确定老年小鼠是否可以通过接种疫苗而受到保护提供了机会。这一探索性项目的首要目标将是确定年龄影响的特定免疫功能，这些功能与丧失对鼠痘的天然和获得性抵抗力有关。这个项目的长期目标是了解在这个探索阶段发现的任何有缺陷的功能背后的基础。此外，我们打算找到新的方法来操纵免疫反应，以恢复老年小鼠的抵抗力，并提高疫苗效力，作为提高老年人疫苗效力的第一途径。

DESCRIPTION (provided by applicant): It is well known that resistance to viral infections and the ability to generate protective immunity following vaccination declines with age. While most of us have been vaccinated and are probably life-long immune to many common viral diseases, we have recently become more aware that emerging infectious diseases are possible, that pandemics with new strains of known viruses such as influenza are likely to occur, and that highly pathogenic microorganisms could be used as weapons. In each of these cases, the non-immune elderly would be at a much higher risk of disease and death than the young. Because the elderly represent a sizable proportion of the world population, understanding the reasons and trying to overcome the consequences of the age- dependent loss of natural and acquired resistance to viral diseases is of major public health interest. However, a direct detailed analysis of the loss of resistance to viral diseases in humans is not possible and appropriate animal models must be used. Mousepox is a frequently lethal disease of the mouse caused by the Orthopoxvirus (OPV) ectromelia virus (ECTV), a disease with remarkable resemblance to human smallpox (caused by the OPV variola virus, VARV) and monkeypox (caused by the homonym OPV). Some strains of mice, such as C57BL/6 (B6), are known to be naturally resistant to mousepox. However, we have recently found that B6 mice lose this resistance as they age. Thus, comparing the immune functions in response to primary ECTV infection of young and aged B6 mice offers an excellent model to understand the age-dependent loss of resistance to viral disease. Furthermore, because mousepox can be prevented with the smallpox vaccine, our new finding opens the opportunity to determine whether aged mice can be protected by vaccination. The overarching goal of this exploratory project will be to pinpoint the specific immune functions affected by age that correlate with the loss of natural and acquired resistance to mousepox. The long-term objective for this project is to understand the underpinnings behind any defective function discovered during this exploratory phase. Furthermore, we intend to find new methods to manipulate the immune response to restore resistance and improve vaccine efficacy in aged mice as a first approach to improve vaccine efficacy in elderly people.