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Development of VSV-based SARS vaccin...

Yale University.

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Development of VSV-based SARS vaccine vectors.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Development of VSV-based SARS vaccine vectors./
Author:	Kapadia, Sagar Umesh.
Description:	113 p.
Notes:	Adviser: John K. Rose.
Contained By:	Dissertation Abstracts International69-05B.
Subject:	Biology, Virology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3317140
ISBN:	9780549658849

Development of VSV-based SARS vaccine vectors.
Kapadia, Sagar Umesh.

Development of VSV-based SARS vaccine vectors. - 113 p.

Adviser: John K. Rose.

Thesis (Ph.D.)--Yale University, 2008.

The SARS outbreak was the first infectious disease of the 21st century to grab global attention. Although it was contained by 2003, the chance of a reemergence is probable because meat markets that expose humans to animals carrying the coronavirus that causes SARS (SARS-CoV) are still operational. Because of a this risk and because of the high death rate associated with SARS, a vaccine would be a useful tool for protection in the event of another outbreak. Therefore, we developed a recombinant VSV-based SARS vaccine using the S protein of SARS-CoV as an antigen. We found that in a mouse model a single dose of the vaccine was able to induce a neutralizing antibody response and protect against SARS-CoV infection. Furthermore, we determined that an antibody response was sufficient for this protection. In order to address safety concerns affiliated with a live viral vaccine, we next attenuated our SARS vaccine so that it could only undergo one round of replication. Such a replication-deficient virus would also allow for quick regulatory approval. We found that one dose of this single-cycle vaccine was able to induce a strong neutralizing antibody response that was indicative of protection. We next constructed and characterized various other potential VSV-based SARS vaccines using other SARS-CoV antigens, M, 3a, N and E. Finally, in an effort to minimize potential exposure to SARS-CoV in the laboratory, we developed a VSV-based pseudotype that can substitute for the SARS-CoV in neutralization assays. Unlike, SARS-CoV, this pseudotype does not require biosafety level 3 containment.

ISBN: 9780549658849Subjects--Topical Terms:

1019068
Biology, Virology.

Development of VSV-based SARS vaccine vectors.
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502 $a Thesis (Ph.D.)--Yale University, 2008.
520 $a The SARS outbreak was the first infectious disease of the 21st century to grab global attention. Although it was contained by 2003, the chance of a reemergence is probable because meat markets that expose humans to animals carrying the coronavirus that causes SARS (SARS-CoV) are still operational. Because of a this risk and because of the high death rate associated with SARS, a vaccine would be a useful tool for protection in the event of another outbreak. Therefore, we developed a recombinant VSV-based SARS vaccine using the S protein of SARS-CoV as an antigen. We found that in a mouse model a single dose of the vaccine was able to induce a neutralizing antibody response and protect against SARS-CoV infection. Furthermore, we determined that an antibody response was sufficient for this protection. In order to address safety concerns affiliated with a live viral vaccine, we next attenuated our SARS vaccine so that it could only undergo one round of replication. Such a replication-deficient virus would also allow for quick regulatory approval. We found that one dose of this single-cycle vaccine was able to induce a strong neutralizing antibody response that was indicative of protection. We next constructed and characterized various other potential VSV-based SARS vaccines using other SARS-CoV antigens, M, 3a, N and E. Finally, in an effort to minimize potential exposure to SARS-CoV in the laboratory, we developed a VSV-based pseudotype that can substitute for the SARS-CoV in neutralization assays. Unlike, SARS-CoV, this pseudotype does not require biosafety level 3 containment.
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