Mutable vaccine for biodefense

描述（由申请人提供）：疫苗接种在预防传染病方面发挥重要作用，因此是生物战的可能解决方案。传统疫苗的固定性质是其成功的主要限制。有些病原体，如艾滋病毒、非典、流感和丙型肝炎，会自然变异，而其他病原体则可能出于军事目的而故意变异。由于免疫反应的发展通常比新的变异慢得多，突变的病原体可以通过疫苗接种逃脱控制，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，由于不可能预测哪些变异将为生物战而故意产生，因此反复接种疫苗不能主动预防“新”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引发针对抗原变异的免疫反应，即可变疫苗。可变疫苗是一种DNA疫苗，其中抗原编码基因的变异频率是典型基因的一百万倍，其变异速度与可变病毒相当。因为突变抗原的出现会预示变异的出现，突变病原体不太可能逃避免疫反应。总体目标是演示可变疫苗的原理证明。为此，流感被用作模型。将生产一种编码可变流感血凝素（HA）基因的载体，并测试产生HA抗原变体的能力。然后将测试这种疫苗是否能够促进针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.