The focus of this proposal is to develop a safe, effective subunit vaccine delivery system. To accomplish this, we will utilize our bacterial commensal vector (BCV) technology. BCV uses the Gram-positive commensal bacteria, Streptococcus gordonii, to express heterologous antigens of interest on its external surface. Phase I human clinical trials indicate that this S. gordonii strain is safe and well-tolerated in humans. Mucosal immunization of mice with S. gordonii expressing vaccinia virus (VV) proteins induced significantly increased vaccinia virus specific antibodies in saliva and serum compared to control animals. Furthermore, serum obtained from immunized mice contained neutralizing antibodies against vaccinia virus. However, immunization of mice with the BCV:VV constructs elicited only partial protection against lethal vaccinia challenge. We hypothesize that co-expression of immunomodulatory molecules by the BCV system will enhance humoral or cellular responses to the encoded antigens, thus providing a safe, effective, and inexpensive subunit vaccine delivery system suitable for use against many viral or bacterial pathogens. To further develop the BCV system the following specific aims are proposed: 1) To enhance the immunogenicity of S. gordonii recombinants by co-expressing cytokines with a model antigen. 2) To evaluate humoral and cellular immune responses to the model antigen after intranasal vaccination of mice with the S. gordonii double recombinants. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
5R43AI072905-02
Application #
7492158
Study Section
Special Emphasis Panel (ZRG1-IMM-K (12))
Program Officer
Challberg, Mark D
Project Start
2007-09-15
Project End
2010-05-31
Budget Start
2008-09-01
Budget End
2010-05-31
Support Year
2
Fiscal Year
2008
Total Cost
$280,538
Indirect Cost
Name
Siga Technologies, Inc.
Department
Type
DUNS #
932651516
City
Corvallis
State
OR
Country
United States
Zip Code
97333
Sockolosky, Jonathan T; Trotta, Eleonora; Parisi, Giulia et al. (2018) Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes. Science 359:1037-1042
Ho, Chia Chi M; Chhabra, Akanksha; Starkl, Philipp et al. (2017) Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling. Cell 168:1041-1052.e18
Sockolosky, Jonathan T; Dougan, Michael; Ingram, Jessica R et al. (2016) Durable antitumor responses to CD47 blockade require adaptive immune stimulation. Proc Natl Acad Sci U S A 113:E2646-54
Sockolosky, Jonathan T; Szoka, Francis C (2015) The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy. Adv Drug Deliv Rev 91:109-24
Ho, Chia Chi M; Guo, Nan; Sockolosky, Jonathan T et al. (2015) ""Velcro"" engineering of high affinity CD47 ectodomain as signal regulatory protein ? (SIRP?) antagonists that enhance antibody-dependent cellular phagocytosis. J Biol Chem 290:12650-63