1.Respiratory Syncytial Virus Fusion Protein-encoding DNA Vaccine Is Less Effective in Conferring Protection against Inflammatory Disease than a Virus-like Particle Platform
Young Man KWON ; Hye Suk HWANG ; Young Tae LEE ; Ki Hye KIM ; Youri LEE ; Min Chul KIM ; Yu Na LEE ; Fu Shi QUAN ; Martin L. MOORE ; Sang Moo KANG
Immune Network 2019;19(3):e18-
Formalin-inactivated respiratory syncytial virus (RSV) vaccination causes vaccine-enhanced disease (VED) after RSV infection. It is considered that vaccine platforms enabling endogenous synthesis of RSV immunogens would induce favorable immune responses than non-replicating subunit vaccines in avoiding VED. Here, we investigated the immunogenicity, protection, and disease in mice after vaccination with RSV fusion protein (F) encoding plasmid DNA (F-DNA) or virus-like particles presenting RSV F (F-VLP). F-DNA vaccination induced CD8 T cells and RSV neutralizing Abs, whereas F-VLP elicited higher levels of IgG2a isotype and neutralizing Abs, and germinal center B cells, contributing to protection by controlling lung viral loads after RSV challenge. However, mice that were immunized with F-DNA displayed weight loss and pulmonary histopathology, and induced F specific CD8 T cell responses and recruitment of monocytes and plasmacytoid dendritic cells into the lungs. These innate immune parameters, RSV disease, and pulmonary histopathology were lower in mice that were immunized with F-VLP after challenge. This study provides important insight into developing effective and safe RSV vaccines.
Animals
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B-Lymphocytes
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Dendritic Cells
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DNA
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Germinal Center
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Immunoglobulin G
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Lung
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Mice
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Monocytes
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Plasmids
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Respiratory Syncytial Virus Vaccines
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Respiratory Syncytial Viruses
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T-Lymphocytes
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Vaccination
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Vaccines, Subunit
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Viral Load
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Weight Loss