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CBER Expertise

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Developing tests to evaluate virus vaccine safety for the nervous system

Principal Investigator: K. M. Carbone, MD
Office / Division / Lab: OVRR / DVP / LMD

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Overview

Public Health Issue: Vaccines are one of the most effective ways of protecting from disease and death following virus infection, by producing protective immune responses to the virus. Many vaccines are based on weakened versions of viruses (attenuated) that ideally are intended to stimulate protective immune responses (efficacy) without producing serious disease (safety). In some cases, vaccines have been found to cause problems with the nervous system (e.g., Urabe mumps vaccine causing meningitis), so it is important to understand and measure the potential risks for certain virus vaccines.

Regulatory Contribution: It is important to be able to predictably evaluate new candidate vaccines for potential safety concerns for the nervous system before widespread use in humans, as well as be able to evaluate consistent manufacturing and safety profiles of licensed vaccines, as needed.

Research Approach: This research program develops new tests for assessing the safety of vaccines for the nervous system, including mumps vaccine, live influenza vaccine and vaccinia-based smallpox vaccines. This effort includes the development of small animal models, tissue culture-based assays and molecular biology based tests.

Mission Relevance and Outcomes: These studies will provide the knowledge and tools for evaluating and supporting the development of safe vaccines.

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Publications

J Virol 2006 Dec;80(24):12141-8
Activation of microglia by Borna Disease Virus infection: an in vitro study.
Ovanesov MV, Sauder C, Rubin SA, Richt J, Nath A, Carbone KM, Pletnikov MV

Vaccine 2006 Mar 24;24(14):2662-8
Serological and phylogenetic evidence of monotypic immune responses to different mumps virus strains.
Rubin S, Mauldin J, Chumakov K, Vanderzanden J, Iskow R, Carbone K

Vaccine 2006 Mar 6;24(10):1530-6
Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.
Atrasheuskaya AV, Neverov AA, Rubin S, Ignatyev GM

J Clin Microbiol 2005 Sep;43(9):4847-51
Mumps virus-specific antibody titers from pre-vaccine era sera: comparison of the plaque reduction neutralization assay and enzyme immunoassays.
Mauldin J, Carbone K, Hsu H, Yolken R, Rubin S

Bioinformatics 2005 Aug 1;21(15):3248-54
A quantitative determination of multi-protein interactions by the analysis of confocal images using a pixel-by-pixel assessment algorithm.
Goucher DR, Wincovitch SM, Garfield SH, Carbone KM, Malik TH
Supplementary Material

J Infect Dis 2005 Apr 1;191(7):1123-8
The rat-based neurovirulence safety test for the assessment of mumps virus neurovirulence in humans: an international collaborative study.
Rubin SA, Afzal MA, Powell CL, Bentley ML, Auda GR, Taffs RE, Carbone KM

Psychiatry Res 2005 Mar 30;134(1):105
Detection of anti-Borna disease virus antibodies by Western blot analysis.
Ghosh M, Sauder C, Carbone KM, Malik TH

Arch Virol 2004 Nov;149(11):2171-86
Susceptibility of Borna disease virus to the antiviral action of gamma-interferon: evidence for species-specific differences.
Sauder C, Herpfer I, Hassler C, Staeheli P

J Neurovirol 2004 Oct;10(5):305-14
Wild-type and attenuated influenza virus infection of the neonatal rat brain.
Rubin S, Liu D, Pletnikov M, McCullers J, Ye Z, Levandowski R, Johannessen J, Carbone K

J Neurovirol 2004 Oct;10(5):267-77
Developmental alterations in serotoninergic neurotransmission in Borna disease virus (BDV)-infected rats: a multidisciplinary analysis.
Dietz D, Vogel M, Rubin S, Moran T, Carbone K, Pletnikov M

Vaccine 2004 Mar 29;22(11-12):1486-93
Mouse neurotoxicity test for vaccinia-based smallpox vaccines.
Li Z, Rubin SA, Taffs RE, Merchlinsky M, Ye Z, Carbone KM

 

 
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