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At least 415 records · Page 23Linked to original sources
PubMed2005

Overview of recent DNA vaccine development for fish.

Since the first description of DNA vaccines for fish in 1996, numerous studies of genetic immunisation against the rhabdovirus pathogens infectious haematopoietic necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV) have established their potential as both highly efficacious biologicals and useful basic research tools. Single small doses of rhabdovirus DNA constructs provide extremely strong protection against severe viral challenge under a variety of conditions. DNA vaccines for several other important fish viruses, bacteria, and parasites are under investigation, but they have not yet shown high efficacy. Therefore, current research is focussed on mechanistic studies to understand the basis of protection, and on improvement of the nucleic acid vaccine applications against a wider range of fish pathogens.

Animals↗
PubMedDate not supplied

The impact of globalization on vaccine development and availability.

Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.

Commerce↗
PubMed2004

Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses.

About 10% of health care professionals vaccinated against hepatitis B virus (HBV) fail to develop protective antibodies. We tested the capacity of peripheral blood lymphocytes from 121 health care professionals, including 76 non-responders, to proliferate to four HBV vaccines, examined the proliferating cells' subset, production of IFN-gamma, IL-4 and IL-10, and for 22 subjects, the cytokine production genotype. Specific proliferative responses to at least one HBV antigen were noted in 75% humoral non-responders. These cells differed from the CD4+ strongly proliferating cells of responders. Non-responders frequently displayed a genotype of high TGF-beta and intermediate IL-10 secretion. Most humoral non-responders to HBV thus develop specific cellular immune responses, eventually liable to protect them against viral infection.

Adult↗
PubMed2003

Prime-boost strategies for malaria vaccine development.

Malaria is an intracellular pathogen, for which an effective vaccine is likely to require induction of cell-mediated immunity. Immunisation approaches that stimulate strong and persistent levels of effector T-cells are being sought by many researchers. DNA vaccines, recombinant protein and viral vectors were amongst the vaccine delivery systems that appeared promising for the generation of cellular immunity, and in some initial studies in small animals this goal was achieved. However, clinical trials of these candidate vaccines when used alone or in repeated homologous boosting regimes have been disappointing, with short-lived low levels of induced specific T-cell responses. Recent years have seen the development of immunisation strategies using a combination of different antigen delivery systems encoding the same epitopes or antigen, delivered at an interval of a few weeks apart. This sequential immunisation approach with different vectors is known as heterologous prime-boosting and is capable of inducing greatly enhanced and persistent levels of CD8+ T-cells and Th1-type CD4+ T-cells compared to homologous boosting. This review will summarise the key pre-clinical studies of prime-boost strategy and outline recent progress in clinical trials of this approach. Possible mechanisms of action and potential improvements to existing delivery systems will be discussed. The prime-boost approach represents an encouraging step towards establishing an effective preventative vaccine to one of the world's greatest killers.

Animals↗
PubMed2005

Recombinant rhabdoviruses: vectors for vaccine development and gene therapy.

The establishment of methods to recover rhabdoviruses from cDNA, so-called reverse genetics systems, has made it possible to genetically engineer rhabdoviruses and to study all aspects of the virus life cycle by introducing defined mutations into the viral genomes. It has also opened the way to make use of the viruses in biomedical applications such as vaccination, gene therapy, or oncolytic virotherapy. The typical gene expression mode of rhabdoviruses, a high genetic stability, and the propensity to tolerate changes in the virus envelope have made rhabdoviruses attractive, targetable gene expression vectors. This chapter provides an overview on the possibilities to manipulate biological properties of the rhabdoviruses that may be important for further development of vaccine vectors and examples of recombinant rhabdoviruses expressing foreign genes and antigens.

Animals↗
PubMed1992

Possible approaches to develop vaccines against hepatitis A.

More than a decade ago, successful replication of hepatitis A virus (HAV) in cell culture opened the way to the development of live attenuated and inactivated vaccine candidates. Serial passages of HAV in cell culture led to attenuation as demonstrated by experiments in non-human primates. Several live vaccine candidates obtained through serial passages have been evaluated in volunteers. Significant improvements in the yield of viral antigen from infected cell cultures stimulated the development of killed vaccine candidates. These formalin-inactivated vaccines contain the viral capsid antigens assembled into viral particles. The immunogenic potential of the vaccine candidates depends strongly on the preservation of the configuration of the capsid proteins. Synthetic peptides covering immunogenic sequences of VP1 as well as soluble capsid proteins expressed as fusion proteins in Escherichia coli were therefore only weakly immunogenic when injected at high concentrations in rabbits. On the other hand, tamarin monkeys immunized with a live recombinant vaccinia expressing P1 were protected against virulent challenge. There are, however, considerable drawbacks related to the use of live vaccinia as a carrier virus. Chimeric polio-HAV VP1 viruses have been constructed. These hybrid viruses were not able to induce an immune response, probably because of configurational constraints of poliovirus on the inserted HAV epitopes. More recently, encouraging data on empty virus particles expressed in baculovirus and vaccinia virus systems have been reported.

Animals↗
PubMed2006

Delipidation of a hepadnavirus: Viral inactivation and vaccine development.

Many viruses including HIV, hepatitis C and hepatitis B, have an outer lipid envelope which maintains inserted viral peptides in the "correct" functional conformation and orientation. Disruption of the lipid envelope by most solvents destroys infectivity and often results in a loss of antigenicity. This communication outlines a novel approach to viral inactivation by specific solvent delipidation which modifies the whole virion rendering it non-infective, but antigenic. Duck hepatitis B virus (DHBV) was delipidated using a diisopropylether (DIPE) and butanol mixture and residual infectivity tested by inoculation into day-old ducks. Delipidation completely inactivated the DHBV (p < 0.001). Delipidated DHBV was then used to vaccinate ducks. Three doses of delipidated DHBV induced anti-DHBs antibody production and prevented high dose challenge infection in five out of six ducks. In comparison, five of six ducks vaccinated with undelipidated DHBV and four of four ducks vaccinated with glutaraldehyde inactivated DHBV were unprotected (p < 0.05). Although this solvent system completely inactivated DHBV, viral antigens were retained in an appropriate form to induce immunity. Delipidation of enveloped viruses with specific organic solvents has potential as the basis for development of vaccines.

Animals↗
PubMed2003

Antigen presentation in vaccine development.

A variety of microorganisms, nutrients or toxins are generally intrude our body through mucosal tissues or skin, where equipment for both preventing their invasions and catching their information to activate internal immune systems for adapting surroundings is arranged. Among the equipment, cells in charge of innate immunity, particularly dendritic cells (DCs), having an excellent capacity for prompt recognition of invaded pathogens via toll-like receptors (TLRs) to alert B and T cells for establishing aquired/adaptive immunity by presenting their processed antigenic fragments, have been paid great attention. These TLR-activated, antigen captured DCs are divided into two groups; one is pathogen-retaining unit and the other is pathogen-controlling unit. The latter DCs present processed antigenic molecules from the pathogens to competent alphabeta T cells together with special containers, such as class I, class II MHC and CD1 to generate specific cellular immunity. The former two MHC molecules can present processed peptide antigens, whereas the last CD1 molecule can present glycolipid/lipid antigens. In contrast, B lymphocytes that captured antigens via their specific immunoglobulin (Ig) receptors present digested peptide fragments with their class II MHC to stimulate suitable CD4(+) helper T cells which in turn secrete various cytokines to efficiently expand and maintain antibody production from that partner B cells to establish humoral immunity. These alphabeta T cells and antibodies, recognize either processed antigenic peptide or glycolipid fragments, and thus, identification of these epitopes enables us to generate artificial pathogen-specific vaccines. Based on the recent findings about precise mechanisms of antigen processing and presentation orchestrated at the surface compartment, future development of vaccines against various pathogens are discussed.

Animals↗
PubMed1997

Cold-adapted live attenuated influenza vaccines developed in Russia: can they contribute to meeting the needs for influenza control in other countries?

It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular. A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and afford-ability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use.

Cold Temperature↗
PubMed2002

Helicobacter pylori type IV secretion, host cell signalling and vaccine development.

Helicobacter pylori is a bacterial pathogen specialised to colonise and persist the gastric mucosa and to cause severe gastroduodenal disease. A major disease-associated bacterial component is a type IV secretion system (TFSS) encoded by the cytotoxin-associated genes pathogenicity island (cagPAI). Among the multiple responses in H. pylori-infected epithelial cells, the induction of proinflammatory cytokines and chemokines, cell spreading and motility associated with the "hum mingbird" phenotype appear strictly dependent on the functional transporter complex in the cagPAI. H. pylori is also capable of occasionally entering epithelial cells and manipulates the host immune system for immune evasion. Attached bacteria actively translocate the CagA protein into epithelial cells by a TFSS-dependent process and translocated CagA undergoes tyrosine phosphorylation in the carboxy terminal EPIYA sequence repeat motif (Y-972) by kinases of the Src family. Furthermore, we have identified a novel TFSS in H. pylori involved in horizontal DNA-transfer. Host cell signalling events and cellular phenotypes provoked by the cagPAI, the investigation of mechanisms related to gastric cancer as well as the development of a Salmonella based live recombinant vaccine are in the focus of additional departmental activities.

Amino Acid Motifs↗
PubMed2000

Rotavirus serotypes: classification and importance in epidemiology, immunity, and vaccine development.

The development and implementation of safe and effective vaccines to prevent the enormous health burden of rotavirus-associated disease is a global public health goal. Human rotaviruses, the major aetiological agents of severe infantile diarrhoea worldwide, display surprisingly diverse and complex serotypic specificities. Ten VP7 serotypes and 7 VP4 serotypes have so far been detected. An increasing number of observations, obtained from analyses of (i) natural rotavirus infections in infants and young children, (ii) experimental rotavirus infections in laboratory animals, and (iii) extensive rotavirus vaccine field trials performed in different populations of various parts of the world, appears to support the concept that serotype-specific antibodies to rotaviruses play an important role in protection against rotavirus-associated illnesses. Thus, the first licensed rotavirus vaccine (RRV-based quadrivalent vaccine) was designed to cover the epidemiologically important VP7 serotype 1, 2, 3, and 4.

Antibodies, Viral↗
PubMed2000

In vitro potency assay for hepatitis A vaccines: development of a unique economical test.

Prior to the official release of each Hepatitis A vaccine lot to the market, a quality control performed by a National Control Authority requires an in vivo or an in vitro potency assay. At the beginning of our work, no standardised in vitro test common to all hepatitis A vaccines was available for both manufacturers and National Control Laboratories. In this study, a unique polyvalent enzyme-linked immunosorbent assay (ELISA) method was developed to appraise all commercially available HAV vaccines. After comparing a direct and an indirect sandwich method with commercial antibodies, the indirect assay was selected and an evaluation of sensitivity, linearity, accuracy and precision was performed before being applied to HAV antigen determination from four different manufacturers. The results are satisfactory and incline us to use routinely this method to release Hepatitis A vaccines.

Biological Assay↗
PubMed1999

Campylobacter vaccine development:a key to controlling enteric diseases.

Worldwide, Campylobacter jejuni is a major cause of diarrhoea and dysentery, with approximately 400 million cases occurring annually. Control of the disease through public health and antibiotic measures is insufficient, and vaccination offers the most promising solution. Infection produces immunity from disease, suggesting that vaccination may produce similar protection. Epidemiological data suggest that there are conserved antigens among serotypes; immunity against which protects against disease. Therefore a monovalent serotype vaccine seems practical. Several antigens on Campylobacter have been found to be immunogenic and, in some cases, associated with virulence. However, none of these proteins have been produced recombinantly in the proper conformation, nor have they been protective in preclinical models. For this reason, live attenuated or inactivated Campylobacter whole cell (CWC) vaccines may be the best approach. Development of an attenuated strain of Campylobacter has been complicated by the fact that the organism is highly transformable. Rec A mutants of Campylobacter have recently been constructed in an attempt to avoid this trait. Such mutants have been made defective in various virulence properties and are being evaluated for safety in preclinical models. Antex Biologics has made an inactivated CWC vaccine using the Company's patented NST (nutriment signal transduction) technology, whereby the cells are grown using physiologically logical conditions to maximise the expression of antigens associated with in vivo virulence. This vaccine has been shown to be safe, immunogenic, and protective in preclinical models of infection. Inclusion of a mucosal adjuvant in the vaccine increases the immunological response to the antigen. Recent Phase I and Phase II clinical trials, using the CWC vaccine formulated with an adjuvant and orally administered, show that the vaccine is safe and immunogenic in human volunteers. The approach used to develop this inactivated whole cell Campylobacter vaccine is also applicable for the rapid development of new vaccines against a variety of mucosal pathogens.

Journal Article↗