Abstract
Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.
Keywords:
F protein; enhanced disease; respiratory syncytial virus; safety; virus-like particle.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Neutralizing / biosynthesis
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Antibodies, Viral
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Humans
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Immunogenicity, Vaccine
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Immunoglobulin G / biosynthesis
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Lung / pathology*
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Lung / virology
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Mice
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Mice, Inbred BALB C
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Mucus
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Respiratory Syncytial Virus Infections / immunology
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Respiratory Syncytial Virus Infections / prevention & control*
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Respiratory Syncytial Virus Infections / virology
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Respiratory Syncytial Virus Vaccines / administration & dosage
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Respiratory Syncytial Virus Vaccines / adverse effects*
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Respiratory Syncytial Virus Vaccines / immunology
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Respiratory Syncytial Virus, Human / immunology
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Th1 Cells
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Th2 Cells
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Vaccination
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Vaccines, Virus-Like Particle / administration & dosage
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Vaccines, Virus-Like Particle / adverse effects
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Vaccines, Virus-Like Particle / immunology*
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Viral Fusion Proteins / administration & dosage
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Viral Fusion Proteins / adverse effects*
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Viral Fusion Proteins / immunology*
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Weight Loss
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Immunoglobulin G
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Respiratory Syncytial Virus Vaccines
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Vaccines, Virus-Like Particle
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Viral Fusion Proteins