The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4(+) T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway
机构：[1]Laboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, United States[2]Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 100045, China[3]Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States[4]Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, United States[5]Department of Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates[6]Department of Biology, Drexel University, Philadelphia, PA 19104, United States[7]Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, Beijing 400715, China科研平台儿科研究所首都医科大学附属北京儿童医院[8]Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, United States[9]Invictus Oncology Pvt. Ltd., Delhi 110092, India.
Vaccination remains the most cost-effective biomedical approach for controlling influenza disease. In times of pandemics, however, these vaccines cannot be produced in sufficient quantities for worldwide use by the current manufacturing capacities and practices. What is needed is the development of adjuvanted vaccines capable of inducing an adequate or better immune response at a decreased antigen dose. Previously we showed that the protein adjuvant rOv-ASP-1 augments influenza-specific antibody titers and survival after virus challenge in both young adult and old-age mice when administered with the trivalent inactivated influenza vaccine (IIV3). In this study we show that a reduced amount of rOv-ASP-1, with 40-times less IIV3 can also induce protection. Apparently the potency of the rOv-ASP-1 adjuvanted IIV3 vaccine is independent of the IIV3-specific Th1/Th2 associated antibody responses, and independent of the presence of HAI antibodies. However, CD4(+) T helper cells were indispensable for the protection. Further, rOv-ASP-1 with or without IIV3 elicited the increased level of various chemokines, which are known chemoattractant for immune cells, into the muscle 4 h after immunization, and significantly induced the recruitment of monocytes, macrophages and neutrophils into the muscles. The recruited monocytes had higher expression of the activation marker MHCII on their surface as well as CXCR3 and CCR2; receptors for IP-10 and MCP-1, respectively. These results show that the rOvASP-1 adjuvant allows substantial antigen sparing of IIV3 by stimulating at the site of injection the accumulation of chemokines and the recruitment of immune cells that can augment the activation of CDA4(+) T cell immune responses, essential for the production of antibody responses. Protection elicited by the rOvASP-1 adjuvanted IIV3 vaccine also appears to function in the absence of MyD88-signaling. Future studies will attempt to delineate the precise mechanisms by which the rOv-ASP-1 adjuvanted IIV3 vaccine works. (C) 2018 Elsevier Ltd. All rights reserved.
基金：
National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R01AI105431]; New York Blood Center
第一作者机构：[1]Laboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, United States[9]Invictus Oncology Pvt. Ltd., Delhi 110092, India.
共同第一作者：
通讯作者：
通讯机构：[1]Laboratory of Molecular Parasitology, Lindsley F Kimball Research Institute, New York Blood Center, New York, NY 10065, United States
推荐引用方式(GB/T 7714)：
Jain Sonia,George Parakkal Jovvian,Deng Wanyan,et al.The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4(+) T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway[J].VACCINE.2018,36(25):3650-3665.doi:10.1016/j.vaccine.2018.05.029.
APA：
Jain, Sonia,George, Parakkal Jovvian,Deng, Wanyan,Koussa, Joseph,Parkhouse, Kaela...&Lustigman, Sara.(2018).The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4(+) T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway.VACCINE,36,(25)
MLA：
Jain, Sonia,et al."The parasite-derived rOv-ASP-1 is an effective antigen-sparing CD4(+) T cell-dependent adjuvant for the trivalent inactivated influenza vaccine, and functions in the absence of MyD88 pathway".VACCINE 36..25(2018):3650-3665
医学