kittolab

 

Objective: To develop novel anitviral vaccines which elicit both cellular and mucosal immune responses.

 

Characteristics of a Good HIV Vaccine:

  • Safe

  • Easily Administered

  • Generates Memory Response

  • Stimulates a T-cell response

  • Protects against a systemic infection

  • Protects against a mucosal infection

Approaches:

  • MHC Approach: Link a piece of the virus known to stimulate the immune system to beta-2microglobulin(beta-2M) and present it to  T-cells.

  • Live Salmonella Approach: Link a piece of the virus to transmembrane protein, express it in  attenuated Salmonella for oral administration as a vaccine.

 

 

 

MHC = Major Histocompatability Complex :

 

The MHC sits on the surface of a cell and is comprised of the heavy chain,    beta-2microglobulin(beta-2M)  and a peptide. The complex acts as a marker signalling to the T-cells of the immune system what is taking place inside the cell.

 

 

 

 

 

First, Link together a peptide from HIV that is known to stimulate the immune system to beta-2microglobulin(beta-2M). Then exchange what you have created with the native peptide and native beta-2microglobulin(beta-2M) . This presents a viral peptide to the T-cells thereby directly priming the immune response for subsequent infection. Thus providing protection against a the virus without being infected with the virus. The exchange can be accomplished with either a DNA vaccine or with a peptide vaccine as shown below.

 

 

 

The Salmonella used in these studies has been attenuated so that it does not produce the harmful toxins that cause Salmonella poisoning. These Salmonella can be administered orally and live without harm in cells in the lower intestinal tract.

The Live Vaccine: First, genetically link a viral peptide to a bacterial transmembrane protein and express it in Salmonella. Since the viral peptide will be expressed on the surface of the Salmonella, host cell proteases can then cleave off the immunogenic peptide. This will enable the host cell to present the peptide to T-cells, thereby directly priming the immune response for subsequent infection. This should provide protection against the virus without being infected with the virus.

 

 

Acknowledgements:

James Caras conducted the initial work on the MHC peptide vaccine, demonstrating that it could stimulate the immune system. Danny Piper, a graduate student, is working on the MHC-DNA vaccine and is optimizing the size of the linker connecting the viral peptide to the beta-2microglobulin(beta-2M)  for both the DNA and peptide version. Aleen Kurien, Mara Vora Check and Stayce Beck are undergraduate students who have provided great assistance.

Mary Susan Burnett Miller, Matthias Hofmann, Brendan Grubbs and Matt Bramble carried out the initial studies on the live AIDS vaccine. Ning Wang has extended the live vaccine approach usinh HIV epitopes.

The Foundation for Research and the UT-NIH Biotechnology Training Grant have provided financial support for this research.