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At least 703 records · Page 39Linked to original sources
PubMed2001

Initial lessons from public-private partnerships in drug and vaccine development.

In recent years, venture capital approaches have delivered impressive results in identifying and funding promising health discoveries and bringing them to market. This success has inspired public sector experiments with "social venture capital" approaches to address the dearth of affordable treatment and prevention for diseases of the developing world. Employing the same focus on well-defined and measurable objectives, and the same type of connections to pool and deploy resources as their for-profit counterparts, social venture capitalists seek to use the tools and incentives of capitalism to solve one of its biggest failures: the lack of drugs and vaccines for diseases endemic to low-income populations. As part of a larger trend of partnerships emerging in health product donation and distribution, public-private partnerships for pharmaceutical development have led research and development (R&D) efforts to generate more accessible and efficacious products for diseases such as malaria, tuberculosis, and AIDS. In this article, three R&D-focused partnerships are explored: the International AIDS Vaccine Initiative; the Medicines for Malaria Venture; and the newly formed Global Alliance for TB Drug Development. The article highlights key elements essential to the success of these ventures.

Anti-HIV Agents↗
PubMedDate not supplied

An auxotrophic live oral Shigella flexneri vaccine: development and testing.

Through transduction, a wild-type strain of Shigella flexneri serotype Y (SFL1) was rendered auxotrophic and dependent on aromatic metabolites that are not available in mammalian tissues. Monkeys that were orally vaccinated with 10(11) bacteria of the transductant strain SFL114 remained healthy when challenged with 10(11) bacteria of wild-type strains of S. flexneri serotypes Y, 1b, and 2a. The safety and immunogenicity of SFL114 were next studied in volunteers who were given either 10(9) or 10(10) SFL114 bacteria orally. Mild intestinal discomfort that lasted for 1-2 days was reported by three (12%) of 25 volunteers given 10(9) live SFL114 bacteria and by 13 (54%) of 24 volunteers given 10(10) live SFL114 bacteria. A local intestinal secretory IgA response to the S. flexneri O-antigen was recorded. The in vitro and in vivo results suggest that the aroD transductant SFL114 possesses properties that are desirable in an oral live candidate vaccine.

Administration, Oral↗
PubMed2000

Analysis of genes expressed at the infective larval stage validates utility of Litomosoides sigmodontis as a murine model for filarial vaccine development.

We used an expressed sequence tag approach to analyze genes expressed by the infective larvae of the rodent filarial parasite Litomosoides sigmodontis. One hundred fifty two new genes were identified, including several proposed as vaccine candidates in studies with human filarial parasites. Our findings have important implications for the use of L. sigmodontis as a model for filarial infection.

Amino Acid Sequence↗
PubMed2004

Type I error and power in noninferiority/equivalence trials with correlated multiple endpoints: an example from vaccine development trials.

Clinical trials necessary for the development of new treatment often require testing of multiple endpoints for equivalence or noninferiority relative to an existing effective standard therapy. An example is a vaccine study with multiple antibody measurements in sera of subjects receiving a combination vaccine such as a pneumococcal vaccine, which contains many different serotypes of the pneumococcal organism. This article describes testing methods for the demonstration of simultaneous marginal equivalence or noninferiority of two treatments on each component of the response vector that follows a multivariate normal distribution. Systematic simulation studies are conducted to evaluate the performance of the testing method and to examine under what conditions the power is substantially different if the multiple endpoints are assumed to be independent when they are actually strongly correlated. Data from an illustrative example are used to describe how the study power can be evaluated in the design of the trials.

Algorithms↗
PubMed2003

Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development.

Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer s disease (AD) was halted as the result of serious neurological complications in some patients. We now provide evidence that AD patients exhibit an enhanced immune response to Abeta and that, contrary to expectations, Abeta antibodies enhance the neurotoxic activity of the peptide. Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. Abeta antibodies were detected in the serum of old APP mutant transgenic mice with plaque-like Abeta deposits, but not in the serum of younger transgenic or nontransgenic mice. Serum from APP mutant mice potentiated the neurotoxicity of Abeta. Our data suggest that a humoral immune response to Abeta in AD patients may promote neuronal degeneration, a process with important implications for the future of vaccine-based therapies for AD.

Aged↗
PubMed1999

Mucosal immunity and tolerance: relevance to vaccine development.

The mucosal immune system of mammals consists of an integrated network of lymphoid cells which work in concert with innate host factors to promote host defense. Major mucosal effector immune mechanisms include secretory antibodies, largely of immunoglobulin A (IgA) isotype, cytotoxic T cells, as well as cytokines, chemokines and their receptors. Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination or natural immunization by a mucosal route can effectively induce immune suppression. The diverse compartments located in the aerodigestive and genitourinary tracts and exocrine glands communicate via preferential homing of lymphocytes and antigen-presenting cells. Mucosal administration of antigens may result in the concomitant expression of secretory immunoglobulin A (S-IgA) antibody responses in various mucosal tissues and secretions, and under certain conditions, in the suppression of immune responses. Thus, developing formulations based on efficient delivery of selected antigens/tolerogens, cytokines and adjuvants may impact on the design of future vaccines and of specific immunotherapeutic approaches against diseases associated with untoward immune responses, such as autoimmune disorders, allergic reactions, and tissue-damaging inflammatory reactions triggered by persistent microorganisms.

Adjuvants, Immunologic↗
PubMed2004

The changing field of vaccine development in the genomics era.

An improved understanding of the human immune system and the genetic make-up of pathogens, together with advances in instrumentation and bioinformatics, have provided new insights into the variation of immune responses to vaccines within the human population. Pathogen variation and the diversity of the immune system components within the human population make the design of universal vaccines difficult. New subunit vaccines that target immunologically similar subgroups of the human population and representative pathogen variants are emerging from research that combines immunomics, pathogen genomics, and high-throughput instrumentation.

Genome, Human↗