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At least 991 records · Page 55Linked to original sources
PubMed2005

Testing of the Biocan B inj. ad us. vet. vaccine and development of the new recombinant vaccine against canine borreliosis.

Verification of the efficacy of Biocan B inj. ad us. vet. (Bioveta, a.s.) was done by challenge testing. Ticks collected in the nature were used as natural vectors of the infection. Six beagles and two control ones were used in the test. Formation of outer surface protein A specific antibodies (OspA antibodies) and borrelia specific immonoglobulins (IgG) was measured by Western blot and EIA in the sera samples. The tissue samples were used for detection of borreliae by cultivation method and dark field microscopy (DFM). Formation of IgG antibodies and OspA antibodies after vaccination was observed. The maximum titer level of antibodies was reached between 21. and 49. day after vaccination and then slowly decreased. Presence of borreliae was detected only in skin biopsies of non-vaccinated dogs. The post mortem tissue samples showed presence of borreliae in all of the samples of the non-vaccinated dogs. The tissues of the vaccinated dogs were not infected with borreliae, except for two samples of dog with low titer levels of OspA antibodies. The development of the new vaccine is based on preparation of recombinant outer surface proteins (e.g. rOspA and rOspC) of B. afzelii, B. burgdorferi and B. garinii origin. Chosen recombinant proteins were successfully expressed in E. coli. The obtained purified proteins are currently being tested on laboratory BALB/c mice. Formation of specific antibodies against some recombinant proteins has been confirmed. These proteins are suitable candidates for preparation of a vaccine prototype and they will be subsequently used in challenge tests.

Animals↗
PubMed2004

Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6.

Human papillomavirus (HPV), particularly type 16 (HPV-16), is present in more than 99% of cervical cancers. The HPV oncoproteins E6 and E7 are constantly expressed and therefore represent ideal targets for HPV vaccine development. We previously developed DNA vaccines encoding calreticulin (CRT) linked to HPV-16 E7 and generated potent E7-specific CD8(+) T-cell immune responses and antitumor effects against an E7-expressing tumor. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a DNA vaccine encoding CRT linked to E6 (CRT/E6). Our results indicated that the CRT/E6 DNA vaccine, but not a wild-type E6 DNA vaccine, generated significant E6-specific CD8(+) T-cell immune responses in vaccinated mice. Mapping of the immunodominant epitope of E6 revealed that an E6 peptide comprising amino acids (aa) 48 to 57 (E6 aa48-57), presented by H-2K(b), is the optimal peptide and that the region of E6 comprising aa 50 to 57 represents the minimal core sequence required for activating E6-specific CD8(+) T lymphocytes. We also demonstrated that E6 aa48-57 contains cytotoxic T-lymphocyte epitopes naturally presented by E6-expressing TC-1 cells. Vaccination with a CRT/E6 but not a CRT/mtE6 (lacking aa 50 to 57 of E6) DNA vaccine could protect vaccinated mice from challenge with E6-expressing TC-1 tumors. Thus, our data indicate that E6 aa48-57 contains the immunodominant epitope and that a CRT/E6 DNA vaccine may be useful for control of HPV infection and HPV-associated lesions.

Amino Acid Sequence↗
PubMed2005

Demand for nonhuman primate resources in the age of biodefense.

The demand for nonhuman primates will undoubtedly increase to meet biomedical needs in this current age of biodefense. The availability of funding has increased the research on select agents and has created a requirement to validate results in relevant primate models. This review provides a description of current and potential biological threats that are likely to require nonhuman primates for the development of vaccines and therapeutics. Primates have been an invaluable resource in the dissection of viral disease pathogenesis as well as in testing vaccine efficacy. DNA vaccine approaches have been studied successfully for Ebola, Lassa, and anthrax in nonhuman primate models. Nonhuman primate research with monkeypox has provided insight into the role of cytokines in limiting disease severity. Biodefense research that has focused on select agents of bacterial origin has also benefited from nonhuman primate studies. Rhesus macaques have traditionally been the model of choice for anthrax research and have yielded successful findings in vaccine development. In plague research, African green monkeys have contributed to vaccine development. However, the disadvantages of current vaccines will undoubtedly require the generation of new vaccines, thus increasing the need for nonhuman primate research. Unfortunately, the current biosafety level (BSL)-3 and BSL-4 facilities equipped to perform this research are limited, which may ultimately impede progress in this era of biodefense.

Animal Experimentation↗
PubMed2002

Immune responses to Neospora caninum and prospects for vaccination.

Developing an effective vaccine against neosporosis presents several interesting challenges. The parasite is spread efficiently from mother to foetus over several generations, and naturally infected cattle do not appear to develop adequate protective immunity. Modulation of the immune response during pregnancy favours parasite survival and multiplication. However, induction of pro-inflammatory responses that are thought to be protective against Neospora caninum would be detrimental to the pregnancy. So, is vaccination a feasible option to control the disease? This article discusses some of these issues and reports on the progress towards a vaccine for neosporosis.

Animals↗
PubMed2001

The contribution of molecular biology to the development of vaccines against nematode and trematode parasites of domestic ruminants.

Rapid developments in molecular biology have had an enormous impact on the prospects for the development of vaccines to control the major nematode and trematode infestations of livestock. Vaccine candidates are purified using conventional protein chemistry techniques but the limitations imposed by the scarcity of parasite material provide an insurmountable barrier for commercial vaccine production by this means. The ability to purify mRNA from different parasite life-cycle stages and to prepare cDNA expression libraries from it has proven central to the identification of immunogenic parasite proteins. Potentially, protective parasite antigens can now be produced in recombinant form in a variety of vectors and this represents a key breakthrough on the road to commercial vaccine production. The contribution of molecular biology to this process is discussed using several examples, particularly in vaccine development against the pathogenic abomasal nematode of sheep and goats, Haemonchus contortus, and the liver fluke of sheep and cattle, Fasciola hepatica. The difficulties of producing recombinant proteins in the correct form, with appropriate post-translational modification and conformation, are discussed as well as emerging means of antigen delivery including DNA vaccination. The opportunities offered by genome and expressed sequence tag analyses programmes for antigen targeting are discussed in association with developing microarray and proteomics technologies which offer the prospect of large scale, rapid antigen screening and identification.

Animals↗
PubMed1998

DNA-antiviral vaccines: new developments and approaches--a review.

Current vaccines can be divided into "live," "recombinant" and "killed" vaccines. Live vaccines are traditionally composed of attenuated viruses or bacteria, selected for their reduced pathogenicity. Recombinant vaccines, driven by a viral or bacterial vector express foreign antigens, or only recombinant proteins injected as antigen. Killed vaccines consist of inactivated whole pathogens. But all these traditional vaccines have some disadvantages: Attenuated live vaccine are able to undergo mutation and as mutated viruses or bacteria can now provoke the diseases against which the vaccine should protect the organism. A further disadvantage of live vaccines is the possibility of shedding which is a real problem especially in veterinary medicine. Clearly, there is a need for better vaccines to protect against diseases without the disadvantages associated with vaccines presently in use. Modern vaccines might be characterized as safe, no risk of reversion to pathogenicity, and they should be stable without the necessity of a "cold chain." Production should be simple, standardized and inexpensive. Vaccine development has now been improved by the ability to use direct inoculations of plasmid DNA encoding viral or bacterial proteins. One of the major benefits of DNA-vaccines, variously termed "DNA-, genetic- or nucleic acid-immunization," is the endogenous synthesis of the encoded protein. Therefore DNA vaccines mimic natural infection and provoke both strong humoral and cellular immune response. This review summarizes new developments and approaches of DNA vaccination and explains the construction of expression plasmids as well as possible mechanisms of immune responses.

Animals↗
PubMed2004

DNA vaccines against anthrax.

DNA vaccination is vaccination at its simplest. Due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development. DNA vaccination against anthrax is an active area of research showing promising results at present, which in the short-term and in the future could form the basis for new advances in multi-agent vaccine development. The anthrax 'model' constitutes an important experimental system for genetic immunisation technology development.

Animals↗
PubMed1997

Induction of antibody response to human tumor antigens by gene therapy using a fusigenic viral liposome vaccine.

Development of effective cancer vaccines would help prevent and control tumor progression. A novel approach of immunizing against tumor antigens is in vivo gene vaccination. We have developed a fusigenic viral liposome vector using HVJ (hemagglutinating virus of Japan) and liposome to deliver human tumor antigen genes effectively to cells in vivo. Plasmids containing the human tumor antigen genes MAGE-1 and MAGE-3 were encapsulated in fusigenic viral liposomes and injected into mice intramuscularly. MAGE-1 and -3 recombinant proteins were used in Western blotting and affinity ELISA for assessment of antibody responses. Mice immunized with MAGE-1 and -3 gene vaccine individually were shown to produce anti-MAGE-1 and -3 IgG antibody responses respectively. Animals immunized with plasmid alone did not induce anti-MAGE-1 or -3 IgG responses. Antibody responses could be enhanced on reimmunization with the gene vaccines. Muscle biopsies taken after vaccine injection were verified to express gene-specific mRNA transcripts. Mice immunized with MAGE-1 or -3 gene vaccines were shown to induce antibodies that could cross-react with the respective recombinant proteins. This study demonstrates that in vivo immunization using HVJ-liposome containing human tumor antigen genes can effectively deliver and induce immune responses to the respective whole proteins.

Animals↗
PubMed2001

Approaches to development of microencapsulated form of the live measles vaccine.

Development of delivery of antigens and antigenic complexes using microcapsules or microgranules made of pH-dependent polymers is one of several high priority directions of modern vaccinology. These polymers should protect the virus from acid gastric medium, dissolve or swell readily in weakly alkaline intestinal medium, in no way decrease the specific activities of viral antigens, promote their penetration into intestinal mucosa, and possess adjuvant properties. The State Research Center Vector and "DELSI" are developing the technology for production of microencapsulated form of the live measles vaccine L-16 viruses for oral administration. The authors have so far succeeded in selecting and characterizing a number of polymers that are promising for microencapsulated vaccine and for testing of virus titers and immune response of experimental samples of a new vaccine in animals. Control of samples in guinea pigs demonstrated that the encapsulated measles virus retained its specific activity and capability for inducing immune response in experimental animals.

Animals↗
PubMed2004

The introduction of new vaccines into developing countries. III. The role of intellectual property.

The development of new vaccines that address the particular needs of developing countries has been proceeding slowly. A number of new public sector vaccine research and development initiatives have been launched to address this problem. These new initiatives find that they often wish to collaborate with the private sector and, in collaborating with the private sector, they must address issues of intellectual property (IP) management. It has not been well understood why IP management is important and how such management by public sector groups can best be conducted. IP management has become very important because vaccine research and development is driven by the regulatory process. The regulatory process has increased the cost of vaccine development to very high levels especially for the highly sophisticated new vaccines currently under development. Thus, investors seek IP protection for the required large investments. Conversely, we assert this concept as a new insight, IP rights are essential for mobilizing the significant funds necessary to meet regulatory requirements. Thus, IP rights are of value not only for investors but also for the public at large. In the absence of public sector mechanisms to carry out the functions that the private sector currently conducts, the public sector needs to increase its sophistication in IP management and needs to identify and implement strategies that will help the public sector to achieve its public health goals, especially for the poor and, among these individuals, the poor in developing countries. This paper suggests some strategies that might be used by the public sector to help achieve its public health goals, especially for the poor.

Charities↗
PubMed2007

Identification of CTL epitopes in hepatitis C virus by a genome-wide computational scanning and a rational design of peptide vaccine.

Developing a peptide-based vaccine for the highly variable hepatitis C virus (HCV) remains a challenging task. Variant viruses not only escape antigen presentation but also persist in a patient as quasi-species. Such variants are often antagonistic to the responding T cell repertoire. To overcome these problems, we herein propose a cocktail vaccine consisting of a few epitope peptides, which make it possible to outpace the emergence of variant viruses. To design such a vaccine, we developed a way to identify HLA-A*2402-binding peptides efficiently by means of the computational scanning of the whole genome of the pathogen. Most of the predicted peptides exhibited strong binding to the HLA-A*2402 molecule, while also inducing CD8 T cell responses from the patients' peripheral blood mononuclear cells (PBMCs). Peptide-induced T cells were capable of lysing HCV-expressing HepG2 cells which process antigens endogenously. The amount of HCV core antigen in the patients' livers suggested that the lytic activity of the peptide-induced T cells was clearly in a range suitable for therapeutic use. If T cells were activated under optimal conditions by high density peptides, then they tended to be relatively tolerant of single amino acid variations for cytolysis. Finally, an analysis of the viral population isolated in Japan suggested no obvious changes due to immune evasion in the viral genome even in a host population highly biased toward HLA-A*2402.

Amino Acid Sequence↗
PubMed1989

New cholera vaccines.

Development of improved cholera vaccines has progressed rapidly in recent years. An oral killed vaccine, designed to evoke antibacterial as well as antitoxic intestinal immunity, has proved to be completely safe and to protect against cholera for at least 3 years. This vaccine also confers substantial though more short-lasting immunity against diarrhoea caused by enterotoxigenic Escherichia coli. Significant progress has also been made towards developing a live attenuated cholera vaccine using recombinant DNA techniques. The advent of effective oral cholera vaccines gives hope for improved control of cholera in the Third World.

Administration, Oral↗
PubMed2003

Thinking downstream to accelerate the introduction of new vaccines for developing countries.

Introduction of new vaccines into public health programs in developing countries requires 'translational research', initiated even during the phase of vaccine development, to generate the evidence base necessary for rational public health decision-making. Translational research encompasses assessments of the local disease burden, demonstration projects of vaccines in realistic public health programs, analysis of the economic impact of vaccine introduction, assessment of community and policy-maker perceptions about the importance of a disease and the need to vaccinate against it, and identification of distribution channels and financial mechanisms for deploying and paying for a new vaccine. In the absence of this background information, even a successful vaccine may risk substantial difficulties and delays in its introduction into programs for the poor in developing countries.

Developing Countries↗
PubMed2002

[Development of vaccine for enterohemorrhagic Escherichia coli infection].

Efforts on the development of vaccines against enterohemorrhagic Escherichia coli (EHEC) infection has been described in this review. Two kinds of vaccines were developed and these have been targeted for in humans and cattle. One vaccine candidate is toxoid, which uses an inactive form of Shiga toxin(Stx). A part of B subunit, each B or A subunit or one or two amino acid mutated holotoxin were developed as a toxoid vaccine candidate. The other candidate was bacterial surface antigen such as a live attenuated EHEC and hybrid between non-toxic LPS and toxoid. A live attenuated vaccine against EHEC O26: H11, O157: H7, O139: H1 were developed. Further a live attenuated vaccine candidate of Vibrio cholerae O1 expressing Stx1-B, Shigella flexneri expressing S. dysenteriae O-antigen and Stx1-B, or Salmonella Typhimurium expressing O111 antigen were developed. Hybrid type vaccine candidates were also developed with O111 LPS and tetanus toxoid, O157 LPS and exotoxin, and O157 LPS and Stx1-B.

Animals↗
PubMed1996

[Current state and problems of the development of malaria vaccine].

The development of vaccines against malaria, particularly the one caused by Plasmodium falciparum, is urgently needed to combat drug-resistant parasites, now spreading in most parts of the tropics. This article reviews molecular and immunological studies on potential candidate antigens at both the sexual stages and the asexual stages of the parasite development and several vaccination trials of SPf66, a synthetic vaccine being currently undertaken in the field. The identification of immunodominant T cell and B cell epitopes and antigen polymorphism/antigenic variation in the parasite, which obviously constitute major problems to be solved before producing effective vaccines, are discussed.

Animals↗