Ross Kathleen, Adams Justin, Loyd Hyelee, Ahmed Shaheen, Sambol Anthony, Broderick Scott, Rajan Krishna, Kohut Marian, Bronich Tatiana, Wannemuehler Michael J, Carpenter Susan, Mallapragada Surya, Narasimhan Balaji
Materials Design and Innovation, University at Buffalo-The State University of New York, Buffalo, New York 14260, United States.
ACS Biomater Sci Eng. 2016 Mar 14;2(3):368-374. doi: 10.1021/acsbiomaterials.5b00477. Epub 2016 Feb 8.
H5N1 influenza virus has the potential to become a significant global health threat, and next generation vaccine technologies are needed. In this work, the combined efficacy of two nanoadjuvant platforms (polyanhydride nanoparticles and pentablock copolymer-based hydrogels) to induce protective immunity against H5N1 influenza virus was examined. Mice received two subcutaneous vaccinations (day 0 and 21) containing 10 μg of H5 hemagglutinin trimer alone or in combination with the nanovaccine platforms. Nanovaccine immunization induced high neutralizing antibody titers that were sustained through 70 days postimmunization. Finally, mice were intranasally challenged with A/H5N1 VNH5N1-PR8CDC-RG virus and monitored for 14 days. Animals receiving the combination nanovaccine had lower viral loads in the lung and weight loss after challenge in comparison to animals vaccinated with each platform alone. These data demonstrate the synergy between polyanhydride nanoparticles and pentablock copolymer-based hydrogels as adjuvants in the design of a more efficacious influenza vaccine.
H5N1流感病毒有可能成为重大的全球健康威胁，因此需要新一代疫苗技术。在这项研究中，研究了两种纳米佐剂平台（聚酸酐纳米颗粒和基于五嵌段共聚物的水凝胶）诱导针对H5N1流感病毒的保护性免疫的联合功效。小鼠在第0天和第21天接受两次皮下接种，接种物包含单独的10μg H5血凝素三聚体或与纳米疫苗平台联合使用。纳米疫苗免疫诱导了高滴度的中和抗体，这些抗体在免疫后70天内持续存在。最后，用A/H5N1 VNH5N1-PR8CDC-RG病毒对小鼠进行鼻内攻毒，并监测14天。与单独使用每个平台接种疫苗的动物相比，接受联合纳米疫苗的动物在攻毒后肺中的病毒载量更低，体重减轻也更少。这些数据证明了聚酸酐纳米颗粒和基于五嵌段共聚物的水凝胶作为佐剂在设计更有效的流感疫苗方面的协同作用。
