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At least 289 records · Page 16Linked to original sources
PubMed1997

Localization by immunoelectron microscopy of antigens of Chlamydia psittaci suitable for diagnosis or vaccine development.

Two different antigens of serotype 1 Chlamydia psittaci were localized using three immunoelectron microscopy techniques: non-embedding, pre-embedding and post-embedding. The antigens had previously been described as being of potential use in diagnosis (80-90 kDa protein region) and vaccine development (110 kDa protein). The results show a direct relationship between the protective capacity of the antigens and their surface localization on the elementary bodies, which are the infectious form of Chlamydia. The 80-90 kDa protein region is located on the surface of reticulate bodies but not of elementary bodies, where it was located periplasmically, while the 110 kDa protein occurs on the surface of both elementary and reticulate bodies.

Animals↗
PubMed1997

Protective immune responses to Theileria annulata of relevance to vaccine development.

A series of projects on Theileria annulata funded by the European Union (STD1/STD2/STD3) have provided convincing evidence that macrophage and natural killer (NK) cell-dependent immune mechanisms may directly control the proliferation of different stages of T. annulata in cattle. The evidence for this conclusion and the implications for vaccine development are discussed in the following paper.

Animals↗
PubMed2002

HPV induced cervical carcinogenesis: molecular basis and vaccine development.

Association of infection with papillomavirus and dysplasia of the cervix uteri has been firmly established. There are only few cervical cancers where no HPV DNA is detectable. The mechanism of epithelial cell immortalization by interaction with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is elucidated. Progression of the HPV infected cell to a malignant phenotype involves further modification of host gene expression and/or mutations. The appearance of chromosomal aberrations can lead to mutational inactivation or loss of tumour suppressor genes (TSG), activation and amplification of oncogenes, with importance for the process of carcinogenesis. Oncogene amplification, with exception of few reports, seems not to be a major mechanism in cervical carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results from CIN and invasive cancer demonstrate alterations at specific chromosomal regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p, 6p, 1lq were frequently found early in tumour development Primary invasive carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q. Useful biological diagnostic and prognostic markers for high-risk HPV infection and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative senescence genes relevant for HPV-induced carcinogenesis are localized on chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist Therefore, immune therapy is an attractive possibility for prevention and therapy of HPV infection. To date, vaccine development has reached clinical evaluation. Prophylaxis aims at the induction of virus neutralizing antibodies to capsid proteins. Virus-like particle vaccines are currently tested in clinical trials. Due to the long lag period between infection and clinical manifestation trials will take a long time until conclusive results are obtained. Mandatory expression of viral and perhaps certain cellular genes in infected epithelial and tumour cells offers targets for therapeutic approaches. Since most dysplasia clears spontaneously the viral infection is immunogenic to some extent. However, in some individuals the immune response has to be stimulated by vaccination in order to be effective. Several strategies are being tested in clinical trials and others are in preclinical development The task will be to circumvent immunosuppressive features of the HPV infected cells.

Chromosome Mapping↗
PubMed2000

DNA vaccines: development, standardization and regulation.

Nucleic acid vaccines contain nonvectored nucleic acids intended to be used as prophylactic vaccines in humans or animals. In addition to the Guidelines Assuring the Quality of DNA Vaccines published by the WHO, further standards for the manufacture and preclinical testing are being developed. Theoretical risks have been taken into account and assessed before human use has been considered. Legal requirements for clinical trials and licensing of nucleic vaccines are in place in Germany and other European member states which allow further testing and development of proprietary medicinal products based on nucleic acids and intended for prophylactic vaccination.

Animals↗
PubMed2004

Ricin: mechanism of toxicity, clinical manifestations, and vaccine development. A review.

Ricin is one of the most potent plant toxins known, and the castor plant from which it is derived, Ricinus communis, is ubiquitous. The harvesting of castor beans exceeds one million tons annually, and ricin is easier to produce than either anthrax or botulinum. As a result, ricin is a convenient, potent, and available toxin for terrorist acts. This paper will review the mechanism of toxicity, major clinical manifestations, treatment, current methods of detection, and vaccine development.

Animals↗
PubMed2003

Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts.

Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I-restricted manner and CD8+ T cell-derived cytokines tumor necrosis factor alpha, interferon gamma, and granulocyte/macrophage colony-stimulating factor-mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.

Animals↗
PubMed2005

Recent advances in contraceptive vaccine development: a mini-review.

Contraceptive vaccines (CV) may provide viable and valuable alternatives to the presently available methods of contraception. The molecules that are being explored for CV development either target gamete production [luteinizing hormone-releasing hormone (LHRH)/GnRH, FSH], gamete function [sperm antigens and oocyte zona pellucida (ZP)], and gamete outcome (HCG). CV targeting gamete production have shown varied degrees of efficacy; however, they either affect sex steroids causing impotency and/or show only a partial rather than a complete effect in inhibiting gametogenesis. However, vaccines based on LHRH/GnRH are being developed by several pharmaceutical companies as substitutes for castration of domestic pets, farm and wild animals, and for therapeutic anticancer purposes such as in prostatic hypertrophy and carcinoma. These vaccines may also find applications in clinical situations that require the inhibition of increased secretions of sex steroids, such as in uterine fibroids, polycystic ovary syndrome, endometriosis and precocious puberty. CV targeting molecules involved in gamete function such as sperm antigens and ZP proteins are exciting choices. Sperm constitute the most promising and exciting target for CV. Several sperm-specific antigens have been delineated in several laboratories and are being actively explored for CV development. Studies are focused on delineating appropriate sperm-specific epitopes, and increasing the immunogenicity (specifically in the local genital tract) and efficacy on the vaccines. Anti-sperm antibody (ASA)-mediated immunoinfertility provides a naturally occurring model to indicate how a vaccine might work in humans. Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects, but may induce oophoritis, affecting sex steroids. They are being successfully tested to control feral populations of dogs, deer, horses and elephants, and populations of several species of zoo animals. The current research for human applicability is focused on delineating infertility-related epitopes (B-cell epitopes) from oophoritis-inducing epitopes (T-cell epitopes). Vaccines targeting gamete outcome primarily focus on the HCG molecule. The HCG vaccine is the first vaccine to undergo Phase I and II clinical trials in humans. Both efficacy and lack of immunopathology have been reasonably well demonstrated for this vaccine. At the present time, studies are focused on increasing the immunogenicity and efficacy of the birth control vaccine, and examining its clinical applications in various HCG-producing cancers. The present article will focus on the current status of the anti-sperm, anti-ZP, anti-LHRH/GnRH and anti-HCG vaccines.

Animals↗
PubMed2004

Leishmaniasis: current status of vaccine development.

Leishmaniasis, a spectrum of diseases caused by various forms of Leishmania has become a major health problem all over the world. Vaccination against leishmaniasis has passed through many developmental stages beginning with the ancient practice of 'leishmanization'. Due to various problems and difficulties associated with traditional vaccines, the interest has been shifted to novel approaches of vaccination like DNA vaccination, vaccination with live vectors encoding leishmanial antigens and finally to designer vaccines. In an effort towards developing an anti-leishmanial vaccine, our laboratory has been working on various genes present in an amplified locus of Leishmania known as the 'LD1 locus'. Two genes, ORFF and BT1 (previously ORFG), are part of the multigenic LD1 locus on chromosome 35. BT1 encodes a biopterin transporter, while the function of ORFF gene product is unknown. Immunization of mice with recombinant ORFF (rORFF) and BT1 proteins, individually, or in combination, conferred partial protection against challenge with Leishmania donovani. We also tested the protective efficacy of ORFF DNA vaccine in BALB/c mice model and found that the level of protection was significantly higher than that of ORFF protein. Protection conferred by ORFF DNA vaccine correlated with significant levels of in vitro splenocyte proliferation and low levels of antigen-specific antibodies. There was a preferential production of IFN-gamma compared to IL-4, which indicated the induction of a protective Th1 response, by the DNA vaccine. Thus, DNA immunization may offer an attractive alternative strategy against leishmaniasis. We present here the current status of vaccine development against leishmaniasis.

Animals↗
PubMed2005

Impact of genetic diversity of HIV-1 on diagnosis, antiretroviral therapy & vaccine development.

HIV-1 strains have diversified extensively through mutation and recombination since their initial transmission to human beings many decades ago in central Africa. The high error rate of HIV reverse transcriptase combined with the estimated in vivo HIV-1 replication rate of ten billion new virions each day leads to extraordinary genetic diversity of HIV. Twenty seven circulating genetic forms of the HIV-1 group M are presently recognized, including 11 subtypes and sub-subtypes, and 16 circulating recombinant forms (CRF). Genotypic analyses have provided a better understanding of the molecular diversity of HIV-1, enabling the detection of emerging HIV-1 variants and improving the tracking of the epidemic worldwide. The rapid evolution of HIV within infected hosts contributes significantly to the elusiveness of this pathogen from host antiviral responses. The complex nature of HIV envelope glycoprotein that is inherently resistant to neutralization, the selective infection, progressive destruction and impaired regeneration of CD4+ T helper cells, generation of cytotoxic T lymphocyte (CTL) escape mutants, together with high genetic diversity with continually evolving HIV variants worldwide, makes design of an effective vaccine a formidable task. Given the rapidity and unpredictability with which HIV-1 genetic forms may propagate in future, a vaccine protective against all major HIV-1 circulating genetic forms is desirable, which could require multivalent formulations. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity and pathogenicity are crucial to the successful design of effective HIV vaccines. In this review, we focus on extensive diversity of HIV-1, emergence of recombinant forms and their impact on diagnosis, antiretroviral therapy, disease progression, transmission, and vaccine development.

AIDS Vaccines↗
PubMed2006

Nucleic acid aptamers as adjuncts to vaccine development.

Nucleic acid 'aptamers', a term derived from the Latin word aptus, 'to fit', are RNA or DNA oligonucleotides that conform to the three-dimensional structure of a selected protein, peptide or small molecules' functional moiety. The 'lock and key' relationship between aptamers and their binding partner permits distinction between closely related but non-identical members of a protein family, or between different functional or conformational states of the same protein. This, along with other properties, separates aptamers from antibodies--the most popular class of molecular recognition tool for the past three decades. Despite the chemical, biological and manufacturing advantages offered by nucleic acid aptamers in a wide variety of conditions, and their generation against a range of clinically relevant targets, including growth factors, transcription factors and coagulation proteins, by two dozen or more companies devoted to the technology platform, only one aptamer, developed for the treatment of wet age-related macular degeneration, is currently available for use in humans. Nevertheless, phase I and II clinical trials for several indications are proceeding with considerable enthusiasm. The potential application of nucleic acid aptamers in novel arenas, including molecular imaging, vaccine development, immunomodulation, decoys for natural RNA-binding events, antiviral therapeutics and both cancer prophylaxis and treatment, is emerging with a pioneering mentality destined to change the paradigm of patient care.

Animals↗
PubMed2001

Pharmacotherapy by intracellular delivery of drugs using fusogenic liposomes: application to vaccine development.

We prepared fusogenic liposomes by fusing conventional liposomes with an ultra-violet inactivated Sendai virus. Fusogenic liposomes can deliver encapsulated contents into the cytoplasm directly in a Sendai virus fusion-dependent manner. Based on the high delivery rates into the cytoplasm, we originally planned to apply the fusogenic liposomes to cancer chemotherapy and gene therapy. We have recently also examined the use of fusogenic liposomes as an antigen delivery vehicle. In terms of vaccine development, cytoplasmic delivery is crucial for the induction of the cytotoxic T lymphocyte (CTL) responses that play a pivotal role against infectious diseases and cancer. In this context, our recent studies suggested that fusogenic liposomes could deliver encapsulated antigens into the cytoplasm and induce MHC class I-restricted, antigen-specific CTL responses. In addition, fusogenic liposomes are also effective as a mucosal vaccine carrier. In this review, we present the feasibility of fusogenic liposomes as a versatile and effective antigen delivery system.

Animals↗
PubMed2004

Textmining in support of knowledge discovery for vaccine development.

Complete genome data of infectious microorganisms permit systematic computational sequence-based predictions and experimental testing of candidate vaccine epitopes. Both, predictions and the interpretation of experiments rely on existing information in the literature which is mostly manually extracted and curated. The growing amount of data and literature information has created a major bottleneck for the interpretation of results and maintenance of curated databases. The lack of suitable free-text information extraction, processing, and reporting tools prompted us to develop a knowledge discovery support system that enhances the understanding of immune response and vaccine development. The current prototype system, Gene expression/epitpopes/protein interaction (GEpi), focuses on molecular functions of HIV-infected T-cells and HIV epitope information, using textmining, and interrelation of biomolecular data from domain-specific databases with MEDLINE abstract-inferred information. Results showed that extraction and processing of molecular interaction, disease associations, and gene ontology-derived functional information generate intuitive knowledge reports that aid the interpretation of host-pathogen interaction. In contrast, epitope (word and sequence) information in MEDLINE abstracts is surprisingly sparse and often lacks necessary context information, such as HLA-restriction. Since the majority of epitope information is found in tables, figures, and legends of full-text articles, its extraction may not require sophisticated natural language processing techniques. Support of vaccine development through textmining requires therefore the timely development of domain-specific extraction rules for full-text articles, and a knowledge model for epitope-related information.

Animals↗
PubMed1994

Copolymer adjuvants in malaria vaccine development.

Protection against virulent challenge with murine Plasmodium yoelii malaria was induced by immunization with whole killed blood-stage parasites in copolymer P1004 and detoxified lipopolysaccharide as adjuvant. Similar immunization with Freund's complete adjuvant and other water-in-oil emulsions failed to protect. Protection was associated with the production of antibody of the IgG2a isotype against epitopes measured by immunofluorescence. Several formulations that did not protect elicited high antibody titers measured by enzyme-linked immunosorbent assays or titers of other isotypes measured by indirect immunofluorescent assay. The results provide additional evidence that the adjuvants influenced both the isotype and specificity of antibody. The implications of these findings for vaccine development are discussed.

Adjuvants, Immunologic↗
PubMedDate not supplied

Cross-linked microparticles as carriers for the delivery of plasmid DNA for vaccine development.

Plasmid DNA was directly encapsulated into biocompatible polymer microparticles via radical polymerization in an inverse emulsion system. Acrylamide-based microspheres 0.2-1 microm in diameter were prepared using an acid-cleavable difunctional monomer. Retention of the DNA payload at physiological pH with complete release under acidic conditions at lysosomal pH was demonstrated. By trapping the plasmid DNA within the cross-linked microparticle, enzymatic degradation was prevented when exposed to serum nucleases. For vaccine development, these delivery vehicles were also investigated for their ability to generate immune responses when delivered to phagocytic cells of the immune system. Encapsulated plasmid DNA demonstrated immunostimulatory activity in macrophages, leading to cytokine secretion of IL-6 with a response approximately 40-fold higher than that achieved with DNA alone.

Animals↗