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At least 451 records · Page 25Linked to original sources
PubMed2003

A genome-based functional screening approach to vaccine development that combines in vitro assays and DNA immunization.

A two-step screening strategy was developed to identify strong immunogenic polypeptides with putative vaccine and/or adjuvant activity. In the first step, a mycobacterial genomic DNA library was screened in vitro to identify plasmids encoding polypeptides that stimulate splenocytes from mycobacteria-immunized mice and T cells from PPD-positive healthy donors to produce interferon-gamma. In the second step, plasmids were selected for their ability to induce protective immunity in a mouse model of tuberculosis following DNA immunization. The potential of this approach is illustrated by the identification of a panel of immunogenic polypeptides that may be used to engineer a new generation of vaccines.

Adjuvants, Immunologic↗
PubMed2003

Influenza virosomes in vaccine development.

Influenza virosomes can be regarded as unilamellar liposomes carrying the spike proteins of influenza virus on their surface. Vaccination with influenza virosomes elicits high titers of influenza-specific antibodies, indicating that HA (and NA) reconstituted into a membranous environment exhibit strong immunogenicity. Moreover, virosomes can be used as presentation systems for unrelated antigens bound to the virosome surface. Because of their intrinsic adjuvant activity, virosomes support antibody formation and induction of T-helper cell responses against such surface-associated antigens. Provided that the fusogenic properties of the reconstituted HA are retained, virosomes can also be used to elicit cytotoxic T-cell responses against encapsulated antigens. Vaccines capable of activating the cellular branch of the immune response can be very important for protection against acute virus infections, especially for viruses with rapidly changing envelope glycoproteins like HIV and influenza virus. Moreover, virosomes can suit as powerful carriers in the development of prophylactic and immunotherapeutic strategies against cancer and premalignant disease. The use of virosomes as commercial influenza vaccine and as commercial adjuvant for a hepatitis A vaccine demonstrates that production of virosomes on an industrial scale is feasible, both technically and economically. The industrial production procedure currently followed has not been designed to retain the functional properties of HA. In fact, several steps in the procedure are probably incompatible with retention of fusion activity. As mentioned previously the fusogenic properties of virosomes are important for CTL activation and might also play a role in the induction of T-helper cell and antibody responses. Therefore, a number of key adaptations in the virosome production protocol will be necessary. Thus improved, virosomes are very attractive devices for the development of highly efficacious vaccines against a range of antigens.

Antigen Presentation↗
PubMed2000

Recent advances in mucosal vaccine development.

Proper stimulation of the mucosal immune system is critical for the effective protection of mucosal surfaces against colonization and invasion of infectious agents. This requires administration of vaccine antigens directly to various mucosal sites. Due to the low absorption efficiency of mucosally delivered vaccines, however, almost all of the currently marketed vaccines are administered parentally. In addition, sub-optimal immune responses are frequently induced by mucosal immunization and the use of mucosal adjuvants is commonly required. As a result, development of successful mucosal vaccines depends largely on the improvement of mucosal antigen delivery and on the discovery of new and effective mucosal adjuvants. In this review, recent advances in both areas are briefly discussed.

Animals↗
PubMed1988

Analysis and genetic manipulation of Shigella virulence determinants for vaccine development.

Shigellosis is a major public health problem in developing countries. Current epidemics of Shigella dysenteriae serotype 1 strains are particularly serious and are characterized by high mortality rates. A high proportion of the isolates are resistant to many of the antibiotics currently in use in these countries, a feature which seriously compromises clinical treatment of the infections. Efficacious vaccines are thus urgently needed. Basic studies on Shigella virulence factors, infections in laboratory models, and host responses has led to the development of several strategies for the production of vaccines. All of these are live oral vaccines involving bacteria capable of at least limited survival in the animal intestine and of carrying selected antigens to the mucosal immune system. One type of vaccine involves non-pathogenic shigellae, attenuated either by introduction of a requirement for aromatic amino acids (aroD) or by loss of the large plasmid that specifies bacterial invasion of the mucosal epithelium. S. dysenteriae 1 strains under development as vaccines need to be engineered to eliminate high level Shiga toxin production, and a rapid and effective method to achieve this was recently elaborated. The second type of vaccine is represented by hybrid strains consisting of a carrier organism, such as an attenuated Salmonella or an Escherichia coli K-12 strain carrying the Shigella invasion plasmid, and the selected foreign antigen that it produces, in all cases so far the Shigella O antigen polysaccharide.

Bacterial Toxins↗
PubMed1990

Synthetic peptides: prospects for vaccine development.

There is great interest in the use of synthetic peptides for vaccine purposes. Chemical synthesis guarantees an unlimited source of chemically stable protein at relatively low cost. Additionally, synthetic peptide antigens have been demonstrated to immunize T helper cells, cytotoxic T cells, and B cells which are reactive with representative native protein antigens. However, a number of obstacles to the use of peptide antigens have also been elucidated. The purpose of this review is to examine our current understanding of peptide antigens as immunogens, and the advantages and disadvantages of their use in vaccine design.

Animals↗
PubMed1995

Whole-virus vaccine development by continuous culture on a complementing host.

We have evaluated an adaptive strategy for generating whole-virus vaccines using a bacteriophage model. Wildtype phage T7 was cultivated in a two-stage continuous stirred-tank reactor (CSTR) utilizing a recombinant E. coli host that constitutively expressed T7 RNA polymerase, an essential enzyme of the early viral metabolism. Over the course of 180 generations a diversity of phage variants emerged, outgrew the wildtype, and were subsequently eclipsed by yet fitter variants, based on host-ranges, restriction patterns, and one-step growth responses of isolated clones. The fittest variant, which required complementation by the recombinant host in order to grow, deleted at least 12 percent of its genome and replicated twice as fast as the wildtype. Moreover, this variant was immunogenically indistinguishable from the wildtype, based on cross-reactivities of antisera raised against both. These results suggest the feasibility of the proposed strategy for the development of safe whole-virus vaccines.

Bacteriophage T7↗