共查询到20条相似文献,搜索用时 15 毫秒
1.
M. A. Julie Westerink Michael A. Apicella 《Springer Seminars in Immunopathology》1993,15(2-3):227-234
Conclusions In 1981 Nisonoff and Lamoyi [24] and Roitt and co-workers [28] suggested that internal image or anti-idiotypic antibodies might be exploited as a new type of vaccine. The anti-idiotype vaccine concept seemed a particularly attractive approach to convert the T-independent carbohydrate antigens into T-dependent antigens.A number of anti-idiotypic antibodies which act as surrogates of carbohydrate antigens have been developed in various laboratories. Other than being internal images of carbohydrate epitopes these anti-idiotypes seem to have little in common. Some are non-protective, some are effective priming agents only and some continue to act as T-independent antigens.The lack of uniformity of these anti-idiotypes is merely a reflection of our limited understanding of the immune system and its interaction with T-independent antigens. Despite the development of fairly effective immunogenic conjugate vaccines the potential application of anti-idiotype vaccines should not be underestimated. These vaccines continue to be of interest in a number of areas. Anti-idiotype vaccines may be converted into thermostable, inexpensive peptide vaccines, especially advantageous in third world countries. Anti-idiotype vaccines may prove to be efficacious in certain genetically defined populations where the conjugate vaccines fail to elicit antibodies [42].Finally, anti-idiotypic antibodies may be extremely useful tools in our understanding of T cell-dependent and -independent B cell activation. 相似文献
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Purified Vi antigens as possible typhoid vaccines 总被引:2,自引:0,他引:2
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Soluble cytokines can act as effective adjuvants in plasmid DNA vaccines targeting self tumor antigens 总被引:3,自引:0,他引:3
There are few vaccination strategies available for the reproducible generation of a cytotoxic T cell (CTL) response, particularly in the setting of immunizing against a tumor antigen. Plasmid-based DNA vaccination offers several advantages as compared to MHC class I peptide-based vaccines or DNA immunization using viral vectors. Plasmid-based DNA vaccines are easily produced, can potentially elicit both an MHC class I and class II response, and have little infectious potential. Plasmid-based vaccines, however, have been poorly immunogenic. The systemic immune response generated after plasmid vaccination relies on in vivo transfection of local antigen presenting cells (APC) and both direct presentation and "cross priming" of antigen by professional and non-professional APC. Therefore, methods to enhance the function of APC, such as simultaneous inoculation with plasmids encoding cytokine genes, has resulted in an enhancement of detectable immunity after vaccination. We questioned whether local application of soluble cytokines would be effective in enhancing the systemic immune response elicited after DNA vaccination. Using a self-tumor antigen model, we vaccinated rats with a plasmid-based rat neu intracellular domain (ICD) DNA construct and either no adjuvant, soluble GM-CSF, or IL-12. We demonstrate that the addition of soluble GM-CSF or IL-12 to rat neu ICD DNA vaccination elicits detectable neu specific T cell immunity; specifically the generation of CTL. Antibodies directed against rat neu were not elicited with this approach, indicating that the neu specific T cell immune response elicited with plasmid DNA was skewed towards cell-mediated rather than humoral immunity. 相似文献
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Live attenuated Salmonella vaccines and their potential as oral combined vaccines carrying heterologous antigens 总被引:4,自引:0,他引:4
C E Hormaeche 《Journal of immunological methods》1991,142(1):113-120
Live attenuated salmonellae are protective, and are candidate vaccines against invasive salmonella infections in man and animals. Different attenuating mutations have been described, and more than one can be incorporated in a vaccine for added safety. Combined salmonella vaccines express target carbohydrate and protein antigens or epitopes from viruses, bacteria and eukaryotic parasites, either within or on the surface of the cell, as capsules, fimbriae, or in the flagellin. Humoral, secretory and cellular responses to the recombinant antigens has been demonstrated. Experimental protection against diseases including streptococcal infection, tetanus, influenza and malaria has been obtained. 相似文献
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Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and
can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization
with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working
in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance
has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous
tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization
against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for
the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma. 相似文献
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DNA vaccines expressing antigens with a stress protein-capturing domain display enhanced immunogenicity 总被引:1,自引:0,他引:1
Summary: An expression system for DNA vaccines is described, in which a fusion protein with an N‐terminal, viral J‐domain that captures heat‐shock proteins (Hsps) is translated in‐frame with C‐terminal antigen‐encoding sequences (of various lengths and origins). The system supports enhanced expression of chimeric antigens (of >800 residues in length) with an extended half life (>8 h). When used as a DNA vaccine, it delivers antigen together with the intrinsic adjuvant activity provided by bound Hsps. We describe the design of vectors for DNA vaccination that support the expression of different immunogenic domains of different origins as large, Hsp‐capturing chimeric fusion antigens. The immunogenicity of the antigens produced by this expression system (when it is built into DNA vaccines) has been characterized in detail, with particular emphasis on priming CD8+ T‐cell responses. We also discuss areas of vaccine research to which the new technology may provide useful contributions. 相似文献
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In recent years, a number of tumor vaccination strategies have been developed. Most of these rely on the identification of tumor antigens that can be recognized by the immune system. DNA vaccination represents one such approach for the induction of both humoral and cellular immune responses against tumor antigens. Studies in animal models have demonstrated the feasibility of utilizing DNA vaccination to elicit protective antitumor immune responses. However, most tumor antigens expressed by cancer cells in humans are weakly immunogenic, and therefore require the development of strategies to potentiate DNA vaccine efficacy in the clinical setting. This review focuses on recent advances in understanding of the immunology of DNA vaccines, as well as strategies used to increase DNA vaccine potency with respect to cytotoxic T-lymphocyte activity. 相似文献
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Towards the development of peptide mimotopes of carbohydrate antigens as cancer vaccines 总被引:6,自引:0,他引:6
Tumor-associated carbohydrate antigens are considered important targets in efforts to develop cancer vaccines. To further enhance vaccine efforts, we are developing peptide mimotopes of tumor-associated carbohydrate antigens that can elicit functional immune responses. Mapping peptide epitopes with anticarbohydrate antibodies can lend to defining structural relationships that can go undetected by screening of carbohydrate antigens alone. Here we contrast reactivity patterns for peptides using monoclonal antibodies (MAbs) directed to the neolactoseries related Lewis Y (LeY) and sialyl-Lewis X (sLeX) antigen and the GD3/GD2 ganglioside antigen. We observe that representative MAbs cross-react with a WRY-containing peptide and that this motif type is isolated by the respective monoclonal in peptide phage display screening. Primary immunization with multiple antigen peptide preparations with QS-21 adjuvant efficiently elicited cytotoxic IgM antibodies for a murine Meth A fibrosarcoma line expressing sLeX. The cytotoxicity of IgG polyclonal response was found to be as effective as IgM in mediating complement-dependent cytotoxicity against the Meth A line. These experiments suggest that peptide mimotopes of the LeY and sLeX tumor-associated carbohydrate antigen and QS-21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma and melanoma patients in the minimal residual disease setting. 相似文献
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The role of CpG in DNA vaccines 总被引:3,自引:0,他引:3
One of the most exciting developments in the field of vaccine research in recent years has been DNA vaccines, with which immune
responses are induced subsequent to the in vivo expression of antigen from directly introduced plasmid DNA. Strong immune
responses have been demonstrated in a number of animal models against many viral, bacterial and parasitic pathogens, and several
human clinical trials have been undertaken. The strong and long-lasting antigen-specific humoral (antibodies) and cell-mediated
(T help, other cytokine functions and cytotoxic T cells) immune responses induced by DNA vaccines appear to be due to the
sustained in vivo expression of antigen, efficient antigen presentation and the presence of stimulatory CpG motifs. These
features are desirable for the development of prophylactic vaccines against numerous infectious agents. Furthermore, the strong
cellular responses are also very desirable for the development of therapeutic DNA vaccines to treat chronic viral infections
or cancer. Efforts are now focusing on understanding the mechanisms for the induction of these immune responses, which in
turn should aid in the optimization of DNA vaccines. This review will focus on the role of CpG motifs in DNA vaccines. 相似文献
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Live, attenuated bacterial vaccines (LBV) are promising candidates for the induction of a broad-based immune response directed at recombinant heterologous antigens and the corresponding pathogen. LBVs allow vaccination through the mucosal surfaces and specific targeting of professional antigen-presenting cells located at the inductive sites of the immune system. A novel approach exploits attenuated intracellular bacteria as delivery vectors for eukaryotic antigen-expression plasmids (so-called DNA vaccines). Candidate carrier bacteria include attenuated strains of Gram-positive and Gram-negative bacteria. These bacteria have been shown to deliver DNA vaccines to human cells in vitro and have also proven their in vivo efficacy in several experimental animal models of infectious diseases and different cancers. The clinical assessment of the safety, immunogenicity and efficacy of these candidate strains will be the next challenging step towards live bacterial DNA vaccines. 相似文献
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Buonaguro L Petrizzo A Tornesello ML Buonaguro FM 《Clinical and Vaccine Immunology : CVI》2011,18(1):23-34
Vaccines represent a strategic successful tool used to prevent or contain diseases with high morbidity and/or mortality. However, while vaccines have proven to be effective in combating pathogenic microorganisms, based on the immune recognition of these foreign antigens, vaccines aimed at inducing effective antitumor activity are still unsatisfactory. Nevertheless, the effectiveness of the two licensed cancer-preventive vaccines targeting tumor-associated viral agents (anti-HBV [hepatitis B virus], to prevent HBV-associated hepatocellular carcinoma, and anti-HPV [human papillomavirus], to prevent HPV-associated cervical carcinoma), along with the recent FDA approval of sipuleucel-T (for the therapeutic treatment of prostate cancer), represents a significant advancement in the field of cancer vaccines and a boost for new studies in the field. Specific active immunotherapies based on anticancer vaccines represent, indeed, a field in continuous evolution and expansion. Significant improvements may result from the selection of the appropriate tumor-specific target antigen (to overcome the peripheral immune tolerance) and/or the development of immunization strategies effective at inducing a protective immune response. This review aims to describe the vast spectrum of tumor antigens and strategies to develop cancer vaccines. 相似文献
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DNA tumor vaccines 总被引:2,自引:0,他引:2
A new generation of vaccines are being developed to induce immune responses that fight off infectious agents, or erradicate cancerous cells. These new vaccines are based on a plasmid vector, which in transfected mammalian cells cause constitutive high-level expression of the target antigen. Expression of the target antigen, in turn, can induce a full-range of immunologic responses, including cell-mediated killing, cell-mediated cytokine release and the production of antigen-specific antibodies. Through molecular techniques, these nucleic acid vaccines can be enhanced to increase target antigen expression and facilitate antigen presentation. Additionally, genetic adjuvants expressed simultaneously with the target antigens can induce the immune responses to disease-associated antigens. The ease with which these genetic vaccines can be generated and the potency of their ability to generate immune-mediated responses make them highly effective, which creates hope for developing effective treatment and prevention of various diseases, most notably cancer. 相似文献
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《Immunology today》1987,8(6):181-185
Vaccination is one of the most cost-effective means of controlling and eradicating infectious disease but at present there is no vaccine against any human parasitic disease. Developments in gene cloning have focused attention on protein antigen vaccines and have opened the way for their large-scale production. There is, however, another class of non-clonable, biologically important molecules, the complex carbohydrates. In this review Emanuela Handman and her colleagues examine the structure and function of carbohydrate antigens of Leishmania, and their possible role in the search for a vaccine against this organism. 相似文献
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Claire-Anne Siegrist Paul-Henri Lambert WHO Collaborating Center for Neonatal Vaccinology 《Springer Seminars in Immunopathology》1997,19(2):233-243
Conclusion DNA vaccines favorably compare to conventional vaccines in their unique capacity to induce, in murine models, adult-like antibody, Th1 and CTL responses at a time of yet significant immune immaturity. Immune responses to DNA vaccines are, however, significantly slower than the one induced by adjuvanted subunit or live vaccines. Although they persist for life in mice, preliminary data in non-human adult primates suggest that this could not be the case in higher mammals. The issue of potential tolerance induction will likely not emerge as a critical feature of human neonatal DNA immunization. However, DNA vaccines are unlikely to prove superior to conventional vaccines in their capacity to circumvent the inhibitory influence of maternal antibodies.Thus, the greater perspectives for neonatal DNA immunization could be found in models where the induction of Th1 and CTL responses are of utmost importance. These are essentially infections with intracellular agents responsible for severe/persistent infections upon early exposure and for which no current efficient and safe conventional vaccine exists. Evaluating neonatal DNA immunization strategies against RSV or herpes viruses, tuberculosis or Chlamydiae therefore emerge as sound priorities. 相似文献
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Song-yue Zheng Bin Yu Ke Zhang Min Chen Yan-Hong Hua Shuofeng Yuan Rory M Watt Bo-Jian Zheng Kwok-Yung Yuen Jian-Dong Huang 《BMC immunology》2012,13(1):1-23