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Patent
Artificial Cell Technologies, Inc. | Date: 2015-05-22

Layer by layer (LBL) construction of products by tangential flow filtration (TFF), or the like, is described, including computer controlled automation of such procedure for production of a multilayer coated core.


Patent
Artificial Cell Technologies, Inc. | Date: 2014-10-08

Multilayer films comprised of polypeptide epitopes and a toll-like receptor ligand. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a virus, bacteria, fungus or parasite.


Patent
Artificial Cell Technologies, Inc. | Date: 2011-07-07

Multilayer films comprise polypeptide epitopes from RSV. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films include at least one designed peptide that includes one or more polypeptide epitopes from RSV. Specifically, the multilayer films include two polypeptide epitopes from RSV, such as an epitope that elicits a specific T-cell response such as a cytotoxic T-cell response, and an epitope that elicits a specific antibody response.


Patent
Artificial Cell Technologies, Inc. | Date: 2016-02-24

Multilayer films comprised of polypeptide epitopes and a toll-like receptor ligand. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a virus, bacteria, fungus or parasite.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 110.92K | Year: 2014

Abstract The ability of the immune system to recognize and initiate an immune response to foreign particles such as bacteria and viruses has generated interest in development of particulate vaccine technologies. We are developing an innovative approach toproduce particulate vaccines via layer-by-layer (LbL) fabrication of synthetic microparticles (MP). We have shown that LbL-MP loaded with epitopes from respiratory syncytial virus (RSV) or Plasmodium falciparum (Pf) elicit potent and balanced humoral and cellular immune responses that protect the immunized host from infection and disease following pathogen challenge. The LbL-MP vaccines are immunogenic and efficacious when administered at low doses (1-10 g) in aqueous suspension without any exogenous adjuvant, thus offering safety advantages over competing vaccine technologies. In this Phase I feasibility study, we will improve the LbL-MP technology by loading the MP into microneedle arrays designed to deliver the payload directly into the skin, a rich res


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 600.00K | Year: 2011

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract illness in infants and the elderly. There is no approved vaccine despite decades of effort. Early attempts to develop a formalin- inactivated vaccine (FI-RSV) resulted in disease enhancement following environmental exposure to RSV. Efforts to develop recombinant subunit vaccines have met with limited success due to poor immunogenicity and short-lived responses. Over the last few years, several avenues of study have suggested that the adverse inflammatory responses associated with RSV infection, and perhaps the failure of the FI-RSV vaccine, are linked to the RSV-G protein which plays a critical role in virus attachment to target cells. RSV-G contains a CX3C chemokine motif that interacts with the CX3CR1 chemokine receptor and appears to elicit an inflammatory Th2-biased immune response that contributes to disease pathogenesis. We have shown that antibody responses to the CX3C motif can reduce virus infectivity, inhibit RSV-G chemokine-modulating activity and reduce lung inflammation following infection. Vaccine designs that elicit an IFN response may also help to reduce the Th2-biased response and lung inflammation associated with RSV infection. In this Phase I project, we will use an innovative approach to produce synthetic nanoparticle vaccines carrying the RSV-G peptide coupled with RSV T-cell target antigens that favor IFN responses. Nanoparticles will be fabricated using layer-by-layer (LbL) deposition of oppositely charged polypeptides, including designed peptides (DP) carrying the antigen payload, to build ultrathin films on solid nano-sized cores. We have shown that vaccines made by this strategy improve the immunogenicityof both T-cell and antibody target epitopes without triggering adverse inflammatory reactions. The current proposal will (1) identify the optimal DP designs for increasing loading and stability of nanoparticles, (2) select LbL nanoparticle vaccine designsbased on potency and phenotype of antibody and T-cell responses induced (with particular emphasis on IFN responses that have been shown to improve protection from RSV disease), and (3) test the biological activity of antibody responses in assays measuringvirus and chemokine neutralization, inhibition of chemotaxis, and protection of mice from viral burden and lung inflammation following challenge with RSV. The RSV-G DP will include a CD4 T-cell epitope that overlaps the chemokine motif, and will be complemented by addition of T-cell target epitopes from RSV-M2 or RSV-F to provide additional IFN modulation of the Th1/Th2 balance. Thus, the novel nanoparticle vaccines produced in this study will have the capacity to elicit multiple mechanisms of protection against RSV infection and aberrant lung inflammation. The deliverable of this project is one or more LbL RSV-G vaccine candidates with demonstrated safety and efficacy in animal models; these candidates will be further developed in a subsequent Phase II project that will complete the steps necessary for Investigational New Drug application filing and eventual clinical testing. The application of this innovative approach to RSV vaccine development will also impact vaccine development for other infectious diseases. PUBLIC HEALTH RELEVANCE: This project will use an innovative nanoparticle technology to produce novel vaccine candidates for respiratory syncytial virus. Since the vaccines contain a portion of the virus responsible for both infection and hostinflammation, vaccine-induced immune responses will not only reduce the rate of RSV infectivity but will also alleviate the lung inflammation associated with RSV disease. A vaccine emerging from this effort will address a large unmet need in infants, children, elderly and immunocompromised patients.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 600.00K | Year: 2010

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 contains 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 central 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 moderated 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 release 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. Immunization 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. falciparum 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 using 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 produce 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 require toxic adjuvants that limit vaccine utility.


Patent
Artificial Cell Technologies, Inc. | Date: 2011-04-13

Disclosed herein are immunogenic compositions comprising a multilayer film comprising two or more layers of polyelectrolytes, wherein adjacent layers comprise oppositely charged polyelectrolytes. A first layer polyelectrolyte comprises an antigenic polypeptide comprising one or more surface adsorption regions covalently linked to one or more antigenic determinant regions, wherein the antigenic polypeptide and the one or more surface adsorption regions have the same polarity. The immunogenic compositions may be employed in methods of eliciting an immune response in a vertebrate organism.


Patent
Artificial Cell Technologies, Inc. | Date: 2013-03-14

Multilayer films comprise polypeptide epitopes from Plasmodium falciparum, specifically a circumsporozoite T1, B or T* epitope. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a Plasmodium protozoan.


Patent
Artificial Cell Technologies, Inc. | Date: 2013-03-14

Multilayer films comprised of polypeptide epitopes and a toll-like receptor ligand. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a virus, bacteria, fungus or parasite.

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