McCormick Anna L, Ross Ted M, Harn Donald A, Mousa Jarrod J
Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Viruses. 2025 Aug 30;17(9):1190. doi: 10.3390/v17091190.
Influenza virus is a leading cause of global morbidity and mortality due to acute lower respiratory infection, even with the widespread use of multiple licensed influenza vaccines. However, antigenic drift during influenza replication can cause vaccine-induced antibodies to poorly neutralize influenza virus, thereby reducing vaccine effectiveness. To help overcome this problem, we leveraged a hydrogel platform with influenza hemagglutinin (HA) protein to induce prolonged antigen exposure. The hydrogel platform, Vaccine Self-Assembling Immune Matrix (VacSIM), in combination with recombinant influenza H1 or H3 HA protein antigens, increased antigen-specific antibody titers in vaccinated mice, which led to decreased disease severity after H1N1 infection for H1 HA-vaccinated mice and decreased lung viral titers after H3N2 challenge for H3 HA-vaccinated mice. Sera collected from mice immunized with VacSIM and HA also showed broader HAI activity, increasing by 1-3 log against a panel of influenza viruses. These results were consistent with the use of cocktail immunization, containing both an H1 and H3 HA, where mice immunized with VacSIM had an increase in antigen-specific antibody titers and decreased disease severity and lung viral titers against H1N1 and H3N2 influenza challenges, respectively. Finally, it was determined that a single immunization with VacSIM and H1 HA could provide protection against lethal H1N1 challenge compared to a group without VacSIM. In summary, we demonstrate that use of the slow-release platform VacSIM can improve the host immune response to vaccination and increase protection against influenza infection.
流感病毒是导致全球因急性下呼吸道感染而发病和死亡的主要原因，即便多种已获许可的流感疫苗已广泛使用。然而，流感病毒复制过程中的抗原漂移可导致疫苗诱导产生的抗体对流感病毒的中和能力不佳，从而降低疫苗效力。为帮助克服这一问题，我们利用了一种含有流感血凝素（HA）蛋白的水凝胶平台，以诱导抗原的持续暴露。该水凝胶平台，即疫苗自组装免疫基质（VacSIM），与重组流感H1或H3 HA蛋白抗原相结合，提高了接种疫苗小鼠体内抗原特异性抗体滴度，这使得接种H1 HA的小鼠在感染H1N1后疾病严重程度降低，接种H3 HA的小鼠在受到H3N2攻击后肺部病毒滴度降低。从用VacSIM和HA免疫的小鼠体内收集的血清也显示出更广泛的血凝抑制（HAI）活性，对一组流感病毒的活性提高了1至3个对数。这些结果与使用同时包含H1和H3 HA的联合免疫接种一致，即用VacSIM免疫的小鼠针对H1N1和H3N2流感攻击的抗原特异性抗体滴度增加，疾病严重程度降低，肺部病毒滴度也降低。最后，确定与未使用VacSIM的组相比，单次用VacSIM和H1 HA免疫可提供针对致死性H1N1攻击的保护。总之，我们证明使用缓释平台VacSIM可改善宿主对疫苗接种的免疫反应，并增强对流感感染的保护。
