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Live Attenuated Vaccines for Respiratory Syncytial Virus

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Replicating Vaccines

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

In the five decades since the identification of respiratory syncytial virus (RSV) as an important pediatric pathogen, no effective vaccine has been developed. Previous attempts to develop inactivated RSV vaccines resulted in vaccine-enhanced disease, resulting in a greater focus on the generation of live attenuated RSV vaccines. However, identifying a live attenuated vaccine candidate that is appropriately attenuated and sufficiently immunogenic has proven to be difficult. Recently, reverse genetics systems have been developed for RSV, allowing researchers to introduce specific mutations into the genomes of recombinant vaccine candidates. These systems provide a means of determining the effects of known attenuating mutations and identifying novel methods of attenuating the virus without decreasing immunogenicity. In addition, different mutations can be combined in a single genome to fine-tune the level of attenuation and immunogenicity to achieve the proper balance in a viable vaccine candidate. Current research into RSV attenuation includes investigation of point mutations responsible for temperature sensitivity, nontemperature-sensitive attenuating mutations, and deletion of nonessential viral genes that play roles in viral RNA synthesis and/or inhibition of innate immune responses. Development of an effective RSV vaccine will likely rely on using reverse genetics systems to optimize the attenuation and immunogenicity of a live vaccine candidate, while preserving viral replication in vitro.

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Acknowledgment

The author would like to gratefully acknowledge the contribution of Kim C. Tran for producing the figures and table for this chapter.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, 16802, USA

    Michael N. Teng

  2. Nanomedicine Research Center, Divisions of Translational Medicine and Allergy & Immunology, Department of Internal Medicine, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA

    Michael N. Teng

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  1. Novartis Vaccines & Diagnostics, Sydney St. 45, Cambridge, 02139, Massachusetts, USA

    Philip R. Dormitzer

  2. Novartis Vaccines & Diagnostics, Inc., Massachusetts Ave. 350, Cambridge, 02139, Massachusetts, USA

    Christian W. Mandl

  3. Novartis Vaccines & Diagnostics S.r.l., Via Fiorentina 1, Siena, 53100, Italy

    Rino Rappuoli

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Teng, M.N. (2011). Live Attenuated Vaccines for Respiratory Syncytial Virus. In: Dormitzer, P., Mandl, C., Rappuoli, R. (eds) Replicating Vaccines. Birkhäuser Advances in Infectious Diseases. Springer, Basel. https://doi.org/10.1007/978-3-0346-0277-8_10

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