Ross Ted M, Gokanapudi Naveen, Ge Pan, Shi Hua, Richardson Robert A, Pierce Spencer R, Sanchez Pedro, Ullah Subhan, De Luca Eliana, Sautto Giuseppe A
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Vaccines (Basel). 2022 Aug 14;10(8):1315. doi: 10.3390/vaccines10081315.
Notwithstanding the current SARS-CoV-2 pandemic, influenza virus infection still represents a global health concern in terms of hospitalizations and possible pandemic threats. The objective of next-generation influenza vaccines is not only to increase the breadth of response but also to improve the elicitation of an effective and robust immune response, especially in high-risk populations. To achieve this second objective, the administration of adjuvanted influenza vaccines has been considered. In this regard, the monitoring and characterization of the antibody response associated with the administration of adjuvanted vaccines has been evaluated in this study in order to shed light on the kinetic, magnitude and subclass usage of antibody secreting cells (ASCs) as well as of circulating antigen-specific serum antibodies. Specifically, we utilized the DBA/2J mouse model to assess the kinetic, magnitude and IgG subclass usage of the antibody response following an intramuscular (IM) or intraperitoneal (IP) immunization regimen with AddaVax-adjuvanted bivalent H1N1 and H3N2 computationally optimized broadly reactive antigen (COBRA) influenza recombinant hemagglutinins (rHAs). While the serological evaluation revealed a homogeneous kinetic of the antibody response, the detection of the ASCs through a FluoroSpot platform revealed a different magnitude, subclass usage and kinetic of the antigen-specific IgG secreting cells peaking at day 5 and day 9 following the IP and IM immunization, respectively.
尽管当前存在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行，但就住院情况和可能的大流行威胁而言，流感病毒感染仍是一个全球卫生问题。新一代流感疫苗的目标不仅是扩大反应广度，还在于改善有效且强大的免疫反应的激发，尤其是在高危人群中。为实现这第二个目标，已考虑使用佐剂流感疫苗。在这方面，本研究评估了与佐剂疫苗接种相关的抗体反应的监测和特征，以阐明抗体分泌细胞（ASC）以及循环抗原特异性血清抗体的动力学、幅度和亚类使用情况。具体而言，我们利用DBA/2J小鼠模型，评估了用AddaVax佐剂的二价H1N1和H3N2计算优化的广泛反应性抗原（COBRA）流感重组血凝素（rHA）进行肌肉内（IM）或腹腔内（IP）免疫接种后抗体反应的动力学、幅度和IgG亚类使用情况。虽然血清学评估显示抗体反应的动力学均匀，但通过FluoroSpot平台检测ASC发现，抗原特异性IgG分泌细胞的幅度、亚类使用情况和动力学不同，分别在IP和IM免疫接种后的第5天和第9天达到峰值。
