Abstract/Details

A flagellin-poxvirus antigen vaccine: Strengths and limitations


2009 2009

Other formats: Order a copy

Abstract (summary)

Bacterial flagellin is a potent adjuvant that enhances adaptive immune responses to a variety of antigens. The vaccinia virus antigens L1R and B5R are highly immunogenic in the context of the parent virus, but recombinant forms of the proteins are only weakly immunogenic. Therefore, we evaluated the response to these antigens when flagellin was used as an adjuvant. Although flagellin promoted a robust antigen-specific humoral response to poxvirus antigens delivered intranasally (i.n.) or intramuscularly (i.m.), intramuscular immunization resulted in significantly high titers of anti-L1R and B5R IgG. Flagellin/poxvirus antigen fusion proteins were more potent than flagellin and L1R and B5R as separate proteins as inducers of a humoral response against the poxvirus antigens. At least three immunizations with flagellin/poxvirus fusion proteins were required to confer protection in mice against challenge with vaccinia virus. Although mice were protected and exhibited only limited signs of disease, they still exhibited significant, but reversible weight loss. When immune mice were depleted of complement using cobra venom factor, 50% of the mice succumbed to vaccinia virus infection. These results demonstrate that flagellin-poxvirus antigen fusion proteins are effective in eliciting protective immunity against vaccinia virus that is dependent, in part, on complement.

We evaluated the efficacy of additional flagellin-poxvirus antigen constructs to promote protective immunity and found that antigens can lose their immunogenicity when inserted into certain regions of flagellin. The loss of immunogenicity is dependent on the individual antigen, and was not the same for all antigens tested. When administering more than one immunogenic fusion protein antigen-specific titers decrease slightly, and the addition of excess flagellin will further decrease titers suggesting that there is a limit to the number of fusion proteins that can be administered in a single vaccine.

Indexing (details)


Subject
Microbiology;
Immunology
Classification
0410: Microbiology
0982: Immunology
Identifier / keyword
Health and environmental sciences; Biological sciences; Flagellin; Immunogenicity; Poxvirus; Vaccines; Vaccinia virus
Title
A flagellin-poxvirus antigen vaccine: Strengths and limitations
Author
Delaney, Kristen N.
Number of pages
94
Publication year
2009
Degree date
2009
School code
0249
Source
DAI-B 70/09, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9781109403275
Advisor
Mizel, Steven B.
University/institution
Wake Forest University, The Bowman Gray School of Medicine
University location
United States -- North Carolina
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3380552
ProQuest document ID
305015593
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305015593
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.