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Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge

Jeanne H Schickli, David C Whitacre, Roderick S Tang

    The Journal of Clinical Investigation
    |March 10, 2015
    PubMed

    Insights

    Researchers developed hybrid virus-like particles (VLPs) displaying the Respiratory Syncytial Virus (RSV) fusion protein epitope. These VLPs successfully elicited protective neutralizing antibodies against RSV in animal models.

    Area of Science:

    • Virology
    • Immunology
    • Vaccine Development

    Background:

    • Respiratory Syncytial Virus (RSV) is a leading cause of severe lower respiratory tract infections in infants and the elderly.
    • Currently, no FDA-approved vaccine exists for RSV, although palivizumab monoclonal antibody offers some protection for high-risk infants.
    • The palivizumab epitope on the RSV fusion (F) protein (F254-277) is a critical target for neutralizing antibodies.

    Purpose of the Study:

    • To develop a novel vaccine strategy for RSV using virus-like particles (VLPs).
    • To genetically engineer hybrid VLPs displaying the palivizumab epitope of the RSV F protein.
    • To assess the immunogenicity and efficacy of these engineered VLPs.

    Main Methods:

    • Genetically inserted the palivizumab epitope and its variants into a woodchuck hepadnavirus core-based VLP (WHcAg-VLP) platform.
    • Generated hybrid VLPs presenting multiple copies of the RSV F protein epitope in an arrayed format.
    • Evaluated VLP recognition by palivizumab in vitro and assessed antibody responses and protection in rodent models.

    Main Results:

    • Several hybrid WHcAg-VLPs containing the RSV F254-277 epitope were recognized by palivizumab.
    • These VLPs induced high titers of neutralizing antibodies in rodents.
    • The elicited antibodies demonstrated protective capacity against RSV challenge in animal models.

    Conclusions:

    • The WHcAg-VLP platform is a viable approach for presenting viral epitopes in a highly immunogenic manner.
    • This proof-of-principle study demonstrates the potential of WHcAg-VLPs for developing an RSV vaccine.
    • The technology may be applicable for eliciting responses to other structural viral epitopes.

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