Abstract
| Grant Number: | 5R42AI051050-03 |
| Project Title: | Lactoferrin as an Adjuvant for Cellular Immunity |
Abstract: DESCRIPTION (provided by applicant): The overall goal of this project is to develop human recombinant Lactoferrin as an adjuvant to BCG to augment cell mediated immunity (CMI) and protect alveolar integrity upon infection with Mycobacterium tuberculosis. Improved nontoxic adjuvants, especially adjuvants capable of inducing CMI, are needed for research in immunology and for development of human and veterinary vaccines. This is especially true for development of vaccines to combat tuberculosis, where efficacy of the bacille Calmette-Guerin strain of M. bovis (BCG) as a vaccine has been unsuccessful to curtail worldwide incidence. Other adjuvants that do induce CMI are much too toxic for use in humans and are being progressively restricted in animals. Lactoferrin is different from microbial adjuvants and from cytokine adjuvants; it is a natural effector molecule that directly participates in host defenses and in the induction of cell mediated immune responses. Phase I studies demonstrate that Lactoferrin as an adjuvant given with BCG enhances delayed type hypersensitivity (DTH) in mice in a dose dependent fashion with no apparent toxicity. Mechanistically, it induces IL-12 and TNF-alpha production by macrophages thereby generating a local environment likely to push immune responses towards development and maintenance of CMI. Our Phase I data indicates Lactoferrin augments BCG vaccination as demonstrated by increased lymphocytic proliferation, and IFN-gamma, IL-2 and IL-12(p40) production towards BCG antigens. Furthermore, aerosol challenge with virulent Mycobacterium tuberculosis (MTB) following Lactoferrin vaccination demonstrated reduction in organism dissemination to spleen, and markedly improved lung pathology that was comparable to Complete Freund's Adjuvant controls. Phase II will specifically address the utility and efficacy of a novel, fully humanized glycoform of recombinant Lactoferrin produced in Pichia pastoris as an adjuvant to augment efficacy of BCG vaccination to subsequent challenge with virulent MTB.
Thesaurus Terms:
Bacillus Calmette Guerin vaccine, cellular immunity, drug screening /evaluation, immunomodulator, lactoferrin, leukocyte activation /transformation, tuberculosis, vaccine evaluation
Mycobacterium tuberculosis, bacterial antigen, interferon gamma, interleukin 12, interleukin 2, recombinant protein
CHO cell, New World Arenavirus, SDS polyacrylamide gel electrophoresis, enzyme linked immunosorbent assay, high performance liquid chromatography, laboratory mouse, matrix assisted laser desorption ionization, polymerase chain reaction, proteomics
| Institution: | PHARMAREVIEW CORPORATION |
| HOUSTON, TX 770833438 |
| Fiscal Year: | 2006 |
| Department: | |
| Project Start: | 01-NOV-2001 |
| Project End: | 30-APR-2008 |
| ICD: | NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES |
| IRG: | ZRG1 |
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