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At least 793 records · Page 44Linked to original sources
PubMed1988

Immunological consequences of HIV infection: advantage of being low responder casts doubts on vaccine development.

Immunosuppression in AIDS might be due to the immune response rather than to the pathogenicity of the virus. The basis of the immunosuppression could be molecular mimicries involving viral gp-110, CD4 molecules, antibodies, and CD4-acceptor sites. Whether an individual develops auto-immunosuppressive responses or mounts a harmless defence against (or coexists with) the virus follows the general rules of lymphocyte repertoire selection. MHC and V region genes and other polymorphic loci, together with the previous state of the immune system, particularly at early developmental periods, are factors that influence the response. Vaccination against gp 110-HIV might thus protect against infection but at the same time cause auto-immunosuppression and disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Recombinant system for overexpression of cholera toxin B subunit in Vibrio cholerae as a basis for vaccine development.

We have constructed an overexpression system in which the gene encoding the B subunit of cholera toxin (CTB) was placed under the control of the strong tacP promoter in a wide host range plasmid. Recombinant nontoxigenic classical and E1 Tor Vibrio cholerae strains of different serotypes harboring this plasmid excreted 10- to 100-fold higher amounts of CTB than any other wild-type or recombinant strain tested and may therefore be useful killed oral vaccine strains. The manipulations to place the CTB gene under tacP also included, by design, the introduction of single enzyme restriction sites for gene fusions to the CTB amino terminus. Cloning into these sites allows construction of CTB-derived hybrid proteins carrying various putative vaccine peptide antigens.

Animals↗
PubMed2006

Unique model of dormant infection for tuberculosis vaccine development.

Most individuals exposed to Mycobacterium tuberculosis become infected but hinder the infectious process in dormant foci, known as latent tuberculosis. This limited infection usually stimulates strong T-cell responses, which provide lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant of Mycobacterium tuberculosis recapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of alpha-crystallin. Mice challenged with the mutant and inoculated with streptomycin for approximately 3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses to M. tuberculosis antigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulent M. tuberculosis. Therefore, infection of mice or other animals (e.g., guinea pigs) with M. tuberculosis strain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of an M. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine.

Animals↗
PubMed1994

Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development.

Neisseria gonorrhoeae infection is limited to the human host. Experimental urethral infection in male volunteers was used to study different aspects of the infection. Urethral installation of a variety of gonococcal variants (10(4)-10(6)) led to infection in 27 subjects, who developed pyuria and shed bacteria in urine before urethritis developed 1-6 days after gonococcal inoculation. The incubation period was affected by the inoculation procedure and size of the inoculum. Subjects were treated with intramuscular ceftriaxone (250 mg) if urethritis developed or at 6 days after inoculation. Urine cultures became negative within several hours of therapy, and symptoms resolved within 1 day of therapy. Infected patients suffered no major complications. Experimental male urethral gonococcal infection provides a unique opportunity to understand the biology and immunology of gonococcal infection and is an efficient method to test gonococcal vaccine candidates.

Adolescent↗
PubMed1998

Papillomaviruses and cervical cancer: pathogenesis and vaccine development.

A subset of human papillomaviruses (HPVs) has been implicated as the principal etiologic agents of cervical cancer. Cervical cancers consistently retain and express two of the viral genes, E6 and E7. Although infection with HPV seems to be necessary, other factors, such as cellular immune function, play an important role in determining whether cervical infection will regress, persist, or progress to cancer. The close relationship between viral infection and cancer makes HPV an attractive target for prophylactic and therapeutic vaccines. Candidate vaccines have been shown to have efficacy in animal models, and human clinical trials are planned or in progress.

Animals↗
PubMed1993

T-cell responses to highly conserved CD4 and CD8 epitopes on the outer membrane protein of bovine leukemia virus: relevance to vaccine development.

Bovine leukemia virus (BLV) is a retrovirus that infects cattle and sheep and may provide a model for studying human leukemia. Cell-mediated immune mechanisms may play a major role in protection against BLV infection. We describe here for the first time the identification of proliferative (CD4) and cytotoxic T-lymphocyte (CD8) epitopes of the gp51 envelope (env) protein of BLV. This protein and a recombinant form expressed by a vaccinia virus construct have been shown to be potential vaccine candidates. A complete series of overlapping peptides, 20 amino acids in length, was prepared to identify epitopes from gp51. These peptides were tested for the ability to elicit peripheral blood lymphocyte proliferation and cytotoxic T-lymphocyte responses in infected and uninfected cattle and sheep. Peptides 51-70 and 61-80 produced a proliferative response in lymphocytes from only uninfected animals (both sheep and cattle), and this was shown by T-cell subset deletion to be a CD4-mediated response. Seven BLV-infected sheep did not show a response to either peptide. Cytotoxic T-lymphocyte activity, however, was associated only with peptides 121-140 and 131-150. In this case, the response was demonstrated to be CD8 dependent and was found only in BLV-infected animals (sheep). Knowledge of the location of these T-cell recognition domains will complement data available on B-cell epitopes in gp51 and may be useful in the design of a subunit vaccine.

Amino Acid Sequence↗
PubMedDate not supplied

[Plasmodium vivax and Plasmodium falciparum gametocyte stages are neglected in vaccine development].

Plasmodium gametocytes are responsible for transmission from the vertebrate host to the mosquito. Plasmodium gametocytes undergo a complex cycle from asexual stages, through a poorly understood process characterized by expression of stage-specific proteins and adhesion molecules. Gametocytes are capable of inducing specific humoral IgG, and cellular responses, which include induction of TNFalpha, IFNgamma and gammadelta+ lymphocyte proliferation, in addition to immune responses to other stages of the parasite (sporozoite, exo-erythrocytic stages, erythrocytic stages). Although transmission-blocking vaccines against Plasmodium do not currently include components against the gametocytes (rather they focus on gametes, zygotes or ookinetes, stages which occur in the mosquito), further understanding of the mechanisms underlying gametocytogenesis and immune responses against these stages may provide additional strategies for more effective transmission inhibition.

Animals↗
PubMed1999

Virulence factors of Helicobacter pylori: implications for vaccine development.

Helicobacter pylori is one of the most common infectious diseases in humans and causes gastritis, peptic ulcer disease and malignant tumours of the stomach. This review discusses how H. pylori can colonize the human stomach, an ecological niche that is protected against all other bacteria. Knowledge about the virulence factors of H. pylori has accumulated rapidly over the last decade. Together with the information contained in the complete H. pylori genome sequence, this knowledge is now being applied in the search for a vaccine against this global pathogen.

Animals↗
PubMed1991

Vaccinia virus: a tool for research and vaccine development.

Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

Animals↗
PubMed2004

Dendritic cells: In the forefront of immunopathogenesis and vaccine development - A review.

Dendritic cellls (DCs) comprise an essential component of the immune system. These cells, as antigen presenting cells (APCs) to naïve T cells, are crucial in the initiation of antigen specific immune responses. In the past years, several DC subsets have been identified in different organs which exert different effects in order to elicit adaptive immune responses. Thus, identification of such DC subsets has led to a better understanding of their distribution and function in the body. In this review, several key properties of the immunobiology, immunopathogenesis and vaccine strategies using DCs will be discussed.

Journal Article↗
PubMed1988

[Gene technology in the diagnosis of viruses and vaccine development].

The development of genetechnological methods since the beginning of the 1970's allowed the molecular cloning of partial or complete viral genomes and the sequencing of their nucleic acids. On this basis, new tools for viral diagnostics are available: molecular probes for hybridization techniques and synthetic peptides or highly purified proteins for the specific detection of antibodies. While the role of synthetic peptides as vaccines seems to be limited, complete viral surface proteins produced by gene technological methods are already used for vaccination in man. The advantages and disadvantages of production in bacteria, in yeast and in higher eukaryotic cells of polypeptides designed as subunit vaccines are discussed. An additional, attractive model is the synthesis of antigens immediately in the host, directed by a recombinant vaccinia virus. Another promising approach is the establishment of potent and safe live vaccines by the introduction of defined mutations or deletions into a viral genome, based on the previous elucidation of the molecular mechanism of attenuation.

Cloning, Molecular↗
PubMed1999

Human tumor antigens: implications for cancer vaccine development.

The adoptive transfer of tumor-infiltrating lymphocytes along with interleukin 2 into autologous patients resulted in the objective regression of tumor in about 30% of patients with melanoma, indicating that these T cells play a role in tumor rejection. To understand the molecular basis of the T cell-cancer cell interaction we and others started to search for tumor antigens expressed on cancer cells recognized by T cells. This led to the identification of several major histocompatibility complex (MHC) class I restricted tumor antigens. These tumor antigens have been classified into several categories: tissue-specific differentiation antigens, tumor-specific shared antigens, and tumor-specific unique antigens. Because CD4+ T cells play a central role in orchestrating the host immune response against cancer, infectious diseases, and autoimmune diseases, a novel genetic approach has recently been developed to identify these MHC class II restricted tumor antigens. The identification of both MHC class I and II restricted tumor antigens provides new opportunities for the development of therapeutic strategies against cancer. This review summarizes the current status of tumor antigens and their potential applications to cancer treatment.

Amino Acid Sequence↗
PubMed1999

DNA pulsed macrophage-mediated cDNA expression library immunization in vaccine development.

cDNA expression library immunization (cDELI), based on the use of a large number of pathogen's cDNA clones, has been previously used in our laboratory in an experimental model of murine Taenia crassiceps cysticercosis. In this study we show that ex vivo immunization of mice with macrophages pulsed in vitro with plasmid DNA containing cDNA expression library (2x10(4) clones) leads to significant reduction of parasite load. Additionally, pathogen-specific proliferation of splenocytes from immunized mice is demonstrated indicating the induction of cellular protective immune response and the efficacy of the proposed strategy to identify vaccine candidate antigens. Our method may represent an attractive tool in vaccine discovery applicable to any host-pathogen system and may be useful especially for the pathogens with large genomes and complicated life cycles.

Animals↗