This characteristic is even more important in deleted live vaccines or recombinant vaccines , which being live vaccines, induce better immune responses than those of the inactivated proteins by expressing antigens with similar characteristics to those of conventional attenuated vaccines. It is also possible to differentiate them. Vaccinated animals show antibodies only against gB, while infected animals have antibodies against gE. DNA vaccines , consisting of a DNA fragment bound to a promoter, evoke both humoral and cell-mediated immunity.
This type of vaccine seems very promising for future therapy. What are the problems that are we are trying to solve? New generation vaccines solve some of the problems usually produced by the use of conventional vaccines. Modification of amino-acid sequences of epitopes to increase affinity for major histocompatibility complex MHC molecules can increase immunogenicity and also qualitatively alter the response — for example, skewing the cytokine profile to improve the antiviral effect.
Recent studies have found that high-avidity cytotoxic T lymphocytes CTLs are much more effective at clearing viral infections, as well as tumours in animal models; these findings provide insights for the design of more effective vaccines. Certain combinations of cytokines and co-stimulatory molecules have been found to act synergistically in amplifying CTL responses or steering the CD4 response towards T helper T H 1 or T H 2 cells; these can be incorporated in vaccines to optimize or customize the response. Strategies to induce mucosal immunity are critical because for CTL to protect against mucosal transmission of viruses, they must reside in the local mucosa furthermore, in the case of HIV, a major reservoir for viral replication is in the gut mucosa, so mucosal CTL might be needed to clear this major reservoir, preventing seeding of the bloodstream.
Gene-based generally DNA vaccines have opened up a new era in vaccinology, with their ease of use and broad applicability, and a number of strategies have been devised recently to increase their efficacy. Dendritic cells have been found to be the key professional antigen-presenting cell needed to initiate a cellular immune response by naive T cells. Strategies are being developed to generate and mature autologous dendritic cells ex vivo to use as autologous vaccines for immunotherapy, or to expand dendritic cells in vivo with cytokines and other agents such as Flt-3 ligand.
Berzofsky, J. Approaches to improve engineered vaccines for human immunodeficiency virus HIV and other viruses that cause chronic infections. Epitope selection and design of synthetic vaccines: molecular approaches to enhancing immunogenicity and crossreactivity of engineered vaccines.
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chapter and author info
Sandberg, J. T cell tolerance based on avidity thresholds rather than complete deletion allows maintenance of maximal repertoire diversity. Pogue, R. Natl Acad. USA 92 , — Sarobe, P. Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2. Parkhurst, M.
Why are additional pneumococcal vaccines needed?
Rosenberg, S. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med. Irvine, K. Recombinant virus vaccination against 'self' antigens using anchor-fixed immunogens. Cancer Res. Ahlers, J. Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence. USA 94 , — High affinity T-helper epitope induces complementary helper and APC polarization, increased CTL and protection against viral infection.
Vaccines for Visceral Leishmaniasis: Hopes and Hurdles
Rammensee, H. MHC ligands and peptide motifs: first listing. Immunogenetics 41 , — Ruppert, J. Prominent role of secondary anchor residues in peptide binding to HLA-A2. Cell 74 , — Alexander, J.
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Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides. Immunity 1 , — La Rosa, C. Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries. Blood 97 , — Slansky, J. Immunity 13 , — Zaremba, S. Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. Fong, L. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. USA 98 , — Tangri, S. Structural features of peptide analogs of human histocompatibility leukocyte antigen class I epitopes that are more potent and immunogenic than wild-type peptide.
NEW GENERATION VACCINES, 3RD EDITION : Shock
Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science , — Alexander-Miller, M. Selective expansion of high or low avidity cytotoxic T lymphocytes and efficacy for adoptive immunotherapy. USA 93 , — Gallimore, A.
Protective immunity does not correlate with the hierarchy of virus-specific cytotoxic T cell responses to naturally processed peptides. Zeh, H. High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. Yee, C. Derby, M. Slifka, M. Nature Immunol. Margulies, D. TCR avidity: it's not how strong you make it, it's how you make it strong. Cawthon, A. Fahmy, T. Increased TCR avidity after T cell activation. A mechanism for sensing low-density antigen. Immunity 14 , — Zheng, L.
Pneumococcal vaccines designed for countries that need them most
Induction of apoptosis in mature T cells by tumour necrosis factor. Nature , — High avidity CTL exploit two complementary mechanisms to provide better protection against viral infection than low avidity CTL. Kawamura, H. Immunization with antigen and interleukin-2 in vivo overcomes Ir gene low responsiveness. Good, M. Recombinant human interleukin-2 IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides.
Correlation of effect with biological activity of IL Disis, M. Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines. Blood 88 , — Belyakov, I. Interplay of cytokines and adjuvants in the regulation of mucosal and systemic HIV-specific cytotoxic T lymphocytes. Xiang, Z. Manipulation of the immune response to a plasmid-encoded viral antigen by coinoculation with plasmids expressing cytokines.
Immunity 2 , — Kim, J. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Iwasaki, A. Scheerlinck, J. Genetic adjuvants for DNA vaccines. Vaccine 19 , — Dranoff, G. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.
USA 90 , — Flexner, C. Prevention of vaccinia virus infection in immunodeficient mice by vector-directed IL-2 expression. Ramshaw, I. Barouch, D. Zhang, X. Immunity 8 , — Ku, C. Waldmann, T. Contrasting roles of IL-2 and IL in the life and death of lymphocytes: implications for immunotherapy. Xin, K. Vaccine 17 , — Mechanisms of cytokine synergy essential for vaccine protection against viral challenge. Chamberlain, R. Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines. Freund, Y. Vaccination with recombinant vaccinia vaccine containing the B co-stimulatory molecule causes no significant toxicity and enhances T cell-mediated cytotoxicity.
Cancer 85 , — Development of a multicomponent candidate vaccine for HIV Vaccine 15 , — Rao, J. IL is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: enhancement by simultaneous B expression. Gurunathan, S. Sin, J. The title of the book does not do justice to its scope.
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It is much more than a description of the new vaccines developed since the previous edition, which was published in Forty percent of the book is devoted to general topics that establish a socioeconomic context for vaccine development i. The quickening pace and scope of stunning scientific advances have facilitated the creation of a new generation of specific vaccines, combined vaccines, sequential prime-boost vaccines, improved adjuvants, viral and bacterial vaccine vectors, and novel delivery systems that use a variety of genetic techniques to manipulate the antigen presentation or the host immunologic response.
Particularly helpful in these introductory sections are the overview chapters J. Kaper and R. The 50 chapters that deal with vaccines for specific diseases are organized into 3 groups. The first group describes new and improved vaccines for use against diseases for which licensed vaccines already exist.
This group includes the polysaccharide conjugate vaccines against meningococcal, H aemophilus influenza , pneumococcal, and enteric bacterial pathogens , as well as new approaches to immunization for influenza, tuberculosis, arboviruses, and cholera. Somewhat surprisingly, there is no chapter on pertussis, although many variations of the acellular vaccine have been developed and are being considered for adult as well as pediatric use.
The second group of chapters describes vaccines against microbial i. These chapters are of uniform high quality and are presented in a sequence that includes a review of the associated pathogen, host-pathogen interactions, and immune correlates of protection, which is followed by a review of vaccination strategies and the vaccine studies to date. Publication schedules precluded the inclusion of a chapter reviewing the very active efforts now being made to develop a vaccine for severe acute respiratory syndrome SARS.
The third group of chapters describes vaccine therapy and vaccines that can be used against cancer and other chronic diseases. The exciting prospect of a vaccine that can be used against human papillomavirus, the cause of cervical cancer, is clearly presented by Boslego, Liu, and Frazer. The chapters about vaccines that can be used against noninfectious diseases such as alzheimer disease, atherosclerosis, multiple sclerosis, type-1 diabetes, and drug addiction, are fascinating science and provide a glimpse into the future.
This excellent book can be considered a standard text in the field of vaccinology. Its focus on basic science and new product development nicely complements another standard text, Vaccines , edited by Plotkin, Orenstein, and Offit [ 1 ], which focuses on applied areas of vaccine recommendations and usage. Textbooks are inherently susceptible to falling behind in a rapidly changing or new field e. Together, these texts and Web sites provide a comprehensive resource for infectious disease experts, vaccine scientists, and students of this important area of medicine and public health.
Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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