Universal Influenza A/B Vaccine

摘要 如果流感的保守抗原具有有效的靶向性，并且 针对这些抗原产生有效的抗病毒免疫反应。DNA疫苗接种是一项吸引人的 然而，提供通用流感疫苗的方法是对保守流感的自然免疫反应 抗原通常很弱，而且大多数在人类身上测试的DNA疫苗都没有诱导出强大的体液免疫。 为了克服开发通用流感DNA疫苗的障碍，我们正在使用新型复合材料 免疫原并与结合了几种工程的下一代基因枪装置一起输送 以及通过增加皮肤细胞和抗原的数量来提高免疫原性的配方创新 呈现表达疫苗抗原的细胞。我们已经取得了令人鼓舞的结果，普遍 甲型流感(UFluA)DNA疫苗。根据这项SBIR建议，我们打算测试一种伴随的普遍流感 B(UFluB)DNA疫苗将创造一种更全面的通用A/B疫苗(UFluA/B)，将提供广泛的 针对能够感染人类的所有A型和B型流感的保护范围。如果我们在以下方面取得成功 证明单一的UFluA/B DNA疫苗可以在小鼠中诱导广泛的反应和保护 第一阶段的努力，我们将推进这一产品的临床前测试下的第二阶段的申请 在那里，我们将研究幼稚和免疫前期雪貂的免疫原性和保护效力，以及安全性和 非人类灵长类动物模型的有效性，该模型在剂量、对DNA的免疫反应方面与人类非常相似 接种疫苗和对流感的易感性。如果成功，这些数据将为Orlance提供强大的临床前 IND数据包将这一战略推进到第一阶段人类临床试验。2.

Abstract Universal influenza vaccines should be possible if conserved antigens of influenza are effectively targeted and effective antiviral immune responses are generated against those antigens. DNA vaccination is an appealing approach for delivering universal influenza vaccines, however, natural immune responses to conserved influenza antigens are typically weak and most DNA vaccines tested in humans have not elicited robust humoral immunity. To overcome the obstacles to developing universal influenza DNA vaccines, we are using novel composite immunogens and delivering them with a next generation Gene Gun device that combines several engineering and formulation innovations that increase immunogenicity by increasing the number of skin cells and antigen presenting cells expressing vaccine antigen. We have already obtained encouraging results with a universal influenza A (UFluA) DNA vaccine. Under this SBIR proposal, we intend to test a companion universal influenza B (UFluB) DNA vaccine to create a more comprehensive universal A/B vaccine (UFluA/B) that will provide broad protective coverage from all influenza A and B types capable of infecting humans. If we are successful at demonstrating that a single UFluA/B DNA vaccine can induce broad responses and protection in mice in the phase I effort, we will advance this this product to preclinical testing under the phase II portion of this application where we will investigate immunogenicity and protective efficacy in naïve and pre-immune ferrets and safety and efficacy in a nonhuman primate model that closely resembles humans in their dosing, immune response to DNA vaccination and susceptibility to influenza. If successful, these data will provide Orlance with a strong preclinical IND data package to advance this strategy to phase I human clinical trials. 2