A mutable vaccine for biodefense

说明(申请人提供)：疫苗接种在预防传染病方面发挥着重要作用，因此是生物战的一种可能解决方案。传统疫苗的固定性质是其成功的一个主要限制。一些病原体，如艾滋病毒、SARS、流感和丙型肝炎自然发生突变，其他病原体可能被故意突变用于军事目的。由于免疫反应的发展通常比新的变种慢得多，突变的病原体可能会逃脱疫苗接种的控制，并迅速产生流行病。目前的战略要求对每一种新发现的病原体进行免疫。然而，由于无法预测哪些变种将被故意用于生物战，因此重复接种疫苗不能主动预防“新的”病原体。拟议的研究将测试一种新型疫苗，这种疫苗将在预期病原体多样化的情况下触发针对抗原变体的免疫反应，这是一种可变疫苗。变种疫苗是一种DNA疫苗，在这种疫苗中，编码抗原的基因的突变频率是典型基因的100万倍，突变速度与变种病毒相当。因为突变抗原的出现会预见到变异的出现，所以突变的病原体不太可能逃避免疫反应。总的目标是证明变种疫苗的原理。为此，流感被用作模型。将生产编码突变的流感血凝素(HA)基因的载体，并将测试产生HA抗原变异体的能力。然后，将测试疫苗是否有能力促进对流感抗原变体的免疫反应。

DESCRIPTION (provided by applicant): Vaccination plays an important role in preventing infectious diseases and is therefore a possible solution for biological warfare. The fixed nature of the traditional vaccine is a major limitation to its success. Some pathogens, such as HIV, SARS, influenza, and hepatitis C naturally mutate and others may be deliberately mutated for military uses. Because immune responses typically develop much more slowly than new variants, mutated pathogens can escape control by vaccination and rapidly generate epidemics. The current strategy calls for immunizing against every newly identified pathogen. However, since it is not possible to predict which variants will be deliberately generated for biological warfare, repeated vaccination cannot proactively protect against "new" pathogens. The proposed research will test a novel type of vaccine that will trigger immune responses directed against antigenic variants in anticipation of pathogen diversification, the mutable vaccine. A mutable vaccine is a DNA vaccine in which the gene coding for the antigen is caused to mutate a million times more frequently than a typical gene, at a rate comparable to that of a mutable virus. Because the appearance of mutant antigens will anticipate the appearance of variants, a mutant pathogen is less likely to evade the immune response. The overall goal is to demonstrate the proof of principle for the mutable vaccine. For this end influenza is used as a model. A vector encoding a mutable influenza hemagglutinin (HA) gene will be produced and ability to generate HA antigenic variants will be tested. The vaccine will then be tested for ability to promote an immune response against antigenic variants of influenza.