Peptide Vaccine for Experimental Autoimmune Myocarditis

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$134,469.00
Award Year:
2003
Program:
SBIR
Phase:
Phase I
Contract:
1R43HL071352-01A1
Award Id:
65758
Agency Tracking Number:
HL071352
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
CEL-SCI CORPORATION, 8229 BOONE BLVD, STE 802, VIENNA, VA, 22182
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
DANIEL ZIMMERMAN
(703) 506-9460
DZIMMERMAN@CEL-SCI.COM
Business Contact:
GEERT KERSTEN
(703) 506-9460
GKERSTEN@CEL-SCI.COM
Research Institution:
n/a
Abstract
DESCRIPTION (provided by the applicant): In A/J Mice Experimental Autoimmune Myocarditis (EAM) can be induced by infection with coxsackie virus B 3 or by immunization with murine or porcine cardiac myosin or a cardiogenic peptide from the murine cardiac myosin (My-l). In all these three cases the mice develop autoantibodies to cardiac myosin, and the disease is characterized by a Th2 phenotype. Previously one of us has shown that the EAM disease process can be blocked by: (1) cobra venom factor (CVF), which depletes complement; or by (2) monoclonal antibodies to the complement receptors involved with the innate immune system; or by (3) antibodies to IL-4 or by (4) Interferon-gamma, which inhibit the Th2 pathway of the inductive immune system. Furthermore, anti-IFN-gamma, treatment exacerbated the EAM. More recently one of our (NRR) studies has demonstrated that IL-10 has a disease inhibiting effect during the later effector phase (after day 10) and not in the early inductor phase (before day 10) using a revised the model which eliminates the Pertussis toxin and results in a slower milder form of disease. Other recent reports also have show a role for IL-10 in disease control in EAM, including use of pentoxifylline which was reported as being used in the human condition. In preliminary studies we have found that pretreatment with a peptide conjugate of the cardiogenic peptide My-l, J-My-l, which is designed to promote a Th1 response against the My-1 antigen, has significantly reduced disease severity. In this study, we intend to examine in more detail and define the role and the effect this conjugate has using the slower progressing EAM model by eliminating the Pertussis toxin. While from a commercialization point the ultimate goal is a product that can be used after disease is diagnosed in this phase I SBIR we will determine whether administration of J-My-1 is beneficial if performed before (1) induction of disease, or (2) during either the induction or (3) effector phases. The specific aims are three Specific Aim 1 To evaluate and compare efficacy of the My-1 L.E.A.P.S. construct, J-My-l, as either an immunotherapeutic vaccine and/or prophylactic treatment for My-1 induced EAM in A/J mice. Specific Aim 2 To evaluate the TH1 and TH2 cytokine(s) profiles and apoptosis markers in spleen lymphocytes obtained from individual NJ mice immunized with J-My-1 to define some aspects of disease induction by the My-1 and the mode of action of J-My-land elucidate the cell population associated with the Thl, Th2 cytokines. The effects of J-My-1 administration on the presence and frequency of this cell type will be evaluated. Our goal is to demonstrate that the severity of EAM can be reduced by J-My-1 administration in animals with EAM.

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government