Synthetic nanocapsule malaria vaccines

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$600,000.00
Award Year:
2010
Program:
SBIR
Phase:
Phase I
Contract:
1R43AI091089-01
Award Id:
95803
Agency Tracking Number:
AI091089
Solicitation Year:
n/a
Solicitation Topic Code:
NIAID
Solicitation Number:
n/a
Small Business Information
ARTIFICIAL CELL TECHNOLOGIES, INC., 5 Science Park, 3rd Floor, NEW HAVEN, CT, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
361522811
Principal Investigator:
THOMAS POWELL
(203) 772-3430
JPOWELL@ARTIFICIALCELLTECH.COM
Business Contact:
DONALD MASTERS
() -
dmasters@artificialcelltech.com
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): The goal of this project is to produce novel synthetic malaria vaccines based on epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the causative agent of human malaria. Malaria is one of the major diseases in the developing world, causing 200-500 million new infections and over 1 million deaths each year, primarily in young children in Africa. While there is no approved vaccine, previous work has shown that the CS protein of the sporozoite stage co ntains a number of candidate vaccine epitopes that are recognized by antibodies and T-cells of protected hosts. These include the conserved antibody epitope of the central repeat region (B) and two T-cell epitopes: T1 which overlaps the N-terminus of the c entral repeat region and T* which is located near the C-terminus of the protein. In preclinical and clinical studies, immunization with the tri-peptide construct T1BT* elicited antibodies to CS that bound to the native protein on the surface of sporozoites , inhibiting their motility and invasion of host hepatocytes, thus disrupting the parasite life cycle and preventing patent blood stage infection responsible for clinical disease. The successes with various CS vaccine strategies have been somewhat moderate d by difficulties in production scale-up, poor immunogenicity, and dose-limiting toxicity of adjuvants. To overcome these issues, an innovative approach will be employed which uses layer-by-layer (LbL) fabrication of artificial biofilms to incorporate the CS epitopes in synthetic nanocapsule vaccines. Current results in multiple model systems show that LbL nanocapsule vaccines elicit potent immune responses following one or two immunizations without adjuvants, avoiding undesirable responses such as the rele ase of inflammatory cytokines. The nanocapsules deliver their antigen payload to dendritic cells via multiple pathways including phagocytosis, leading to presentation of Class II-restricted epitopes and cross-presentation of Class I-restricted epitopes. Im munization with LbL nanocapsules elicits balanced T-cell responses including both IFN and IL-4 ELISPOTs, and effector CTL activity. The immune responses elicited by LbL nanocapsules conspicuously do not include antibody responses to the matrix polypeptides used to produce the biofilm, thereby avoiding the so-called vector or carrier effect that has hampered development of many viral vectored vaccines. In this project, mono- and multivalent LbL nanocapsules containing the T1, B, and/or T* epitopes of P. falc iparum CS, or the CTL epitope of P. berghei, will be designed and fabricated. Immunogenicity will be studied in mice by monitoring ELISPOT and in vivo CTL responses to the T-cell epitopes and antibody responses to the B epitope. Efficacy will be studied us ing transgenic P. berghei (mouse pathogen) expressing a hybrid CS containing the B epitope from P. falciparum CS (PfPb) to measure protective antibodies, or wild-type P. berghei to measure protective CD8+ T-cell responses. This project will yield synthetic nanocapsule vaccine candidates that elicit potent CS-specific immune responses and provide protection from malaria without the use of toxic adjuvants. PUBLIC HEALTH RELEVANCE: This project utilizes an innovative vaccine fabrication technology to produc e efficacious vaccines for malaria. These vaccines are made of biofilms of materials safe for human use and are fabricated by synthetic chemistry methods with no animal or cell culture products or by-products. The vaccines are potent, safe, and do not requ ire toxic adjuvants that limit vaccine utility.

* 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