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At least 937 records · Page 52Linked to original sources
PubMed2003

Schistosomiasis vaccines.

While there are many challenges in vaccine development, none is greater than that of developing vaccines against large metazoan parasites such as schistosomes, the parasitic worms that are responsible for schistosomiasis. Initial optimism stemming from the identification of the first vaccine candidate antigens that gave protection in animals has been dashed by the failure, as yet, of any of the vaccine candidate antigens to enter Phase III clinical trials. Now, despite an improved understanding of the biology of the parasites and of the immune responses they stimulate in naturally exposed populations, the vaccine effort is stalled. The control effort has switched heavily in favour of the wider use of conventional chemotherapy with praziquantel, which is now affordable by all but the poorest countries. Disagreements among researchers in the schistosome field as to whether or not a vaccine is needed have not helped convince funding agencies that schistosomiasis vaccines, rather than drugs, should be a priority. With the schistosome genome projects at an advanced stage plus the power of the proteomics, perhaps it is still too early to call time on schistosome vaccine development.

Animals↗
PubMed2001

Random-peptide libraries and antigen-fragment libraries for epitope mapping and the development of vaccines and diagnostics.

Random peptide libraries and antigen-fragment libraries (also known as gene-fragment libraries) have been used to identify epitopes on protein antigens. These technologies promise to make significant contributions to diagnostic and vaccine development. Researchers in a number of labs have shown that phage selected from libraries with protective antibodies, raised against whole antigen, can be used as immunogens to stimulate antibody responses that bind native antigen and provide protection in vivo. Others have used the sera of patients with idiopathic diseases to screen libraries, and by this approach have identified candidate antigens involved in immune disease. These may prove useful for diagnosis and, possibly, in determining disease etiology.

Antibodies↗
PubMed2005

Human papillomavirus vaccines in development: if they're successful in clinical trials, how will they be implemented?

INTRODUCTION: There are some 30-40 genotypes of human papillomavirus (HPV) that cause anogenital lesions in humans, primarily cervical, vaginal, and vulvar dysplasias and cancer in women, anal dysplasias in some men, and genital warts in both sexes. METHODS: Both GlaxoSmithKline and Merck companies are developing vaccines for the prevention of HPV infection. RESULTS: Both vaccines stimulate an antibody response against HPV types 16 and 18; the Merck vaccine also include HPV types 6 and 11. CONCLUSIONS: This report focuses on progress with both prophylactic vaccines and introduces strategies for global immunization.

Clinical Trials as Topic↗
PubMed2006

Modifications increasing the efficacy of recombinant vaccines; marked increase in antibody titers with moderately repetitive variants of a therapeutic allergy vaccine.

Development of vaccines targeting important self-molecules like tumor antigens, IgE, cytokines or other regulatory molecules, brings about challenges that are not met in classical vaccine development. Tolerance inducing mechanisms reduce the levels of therapeutic antibodies in the vaccinated subject, and anti-self antibody titers are frequently more than 50-fold lower than the anti-non-self response to the carrier. In order to overcome this limitation in efficacy we have explored various methods to enhance the immunogenicity of the vaccine antigen. Vaccination with a molecule containing two IgE Cepsilon3 domains and thereby a low level of repetitiveness markedly increased the efficacy. The anti-IgE antibody titers in the animals treated with the dimeric vaccine antigen were 4.5, 5 and 8 times higher than in the animals treated with the monomer, in three independent experiments. In addition, this increase in efficacy was not masked by the use of potent adjuvants. The effect persisted even in the presence of Freunds or Montanide ISA 51, two mineral oil based adjuvants. This in contrast to most Toll-like receptor (TLR) agonists, which appear to enhance the immune response only when administrated together with weak adjuvants. This clearly shows that the introduction of a moderately repetitive structure is enough to substantially increase the efficacy of a therapeutic vaccine.

Adjuvants, Immunologic↗
PubMed2002

Brucella abortus RB51: enhancing vaccine efficacy and developing multivalent vaccines.

Brucella abortus vaccine strain RB51 is an attenuated, stable rough mutant that is being used in many countries to control bovine brucellosis. Our earlier study demonstrated that the protective efficacy of strain RB51 can be significantly enhanced by overexpressing Cu-Zn superoxide dismutase (SOD), a homologous protective antigen. We have also previously demonstrated that strain RB51 can be engineered to express heterologous proteins and mice vaccinated with such recombinant RB51 strains develop a strong Th1 type of immune response to the foreign proteins. The present study is aimed at combining these two characteristics to generate new recombinant RB51 vaccines with enhanced abilities to protect against brucellosis and simultaneously able to protect against infections by Mycobacterium spp. We constructed two recombinant RB51 strains, RB51SOD/85A which overexpresses SOD with simultaneous expression of the 85A, a protective protein of Mycobacterium spp., and RB51ESAT which expresses ESAT-6, another protective protein of M. bovis, as a fusion protein with the signal sequence and few additional amino terminal amino acids of SOD. Mice vaccinated with these recombinant strains developed specific immune responses to the mycobacterial proteins and significantly enhanced protection against Brucella challenge compared to the mice vaccinated with strain RB51 alone.

Animals↗
PubMed1997

Development of a malaria vaccine.

Development of an effective malaria vaccine poses a major scientific challenge both in the laboratory and in the field. Such a vaccine is necessary because of the massive disease burden of malaria in the developing world, the global spread of drug resistance, and the difficulty of sustainable control of the mosquito vector. Animal models have shown the immunological feasibility of vaccines targeted against different stages of parasite development, and studies in human volunteers have shown that a recombinant protein vaccine can protect against challenge with the homologous strain of parasite. However, both natural and vaccine-induced immunity are hampered by the remarkable capacity of the parasites to vary critical antigenic structures; large field trials of a synthetic peptide vaccine gave equivocal results. In an attempt to overcome the dual difficulty of poor immunogenicity and parasite diversity, much experimental work is now focused on complex antigenic constructs, delivered as DNA vaccines or in live vectors such as vaccinia, with multiple targets at each stage of parasite development.

Animals↗
PubMed1987

The development of novel hepatitis B vaccines.

Development of vaccines against viral hepatitis B has proceeded along four main lines. (1) Human plasma-derived vaccines are safe, effective and are now in general use. (2) Subunit polypeptide vaccines formulated in micelles have reached the stage of clinical trials. (3) Recombinant DNA vaccines have been produced in prokaryotic and eukaryotic cells, notably in yeast. The yeast-derived recombinant vaccines have proved safe and effective in extensive clinical trials, eliciting antibodies which in quantity and specificity are equal to those elicited by plasma-derived vaccine. DNA recombinant has also been applied to the development of hybrid and vaccinia virus vaccines which are capable of immunological "priming", and other hybrid virus vaccines are under development. (4) Finally, chemical synthesis has succeeded in producing small peptides which include specific epitopes eliciting antibody responses in experimental animals. Such chemically synthesized preparations offer a prospect of ultimately producing multivalent synthetic vaccines against several viruses, bacteria and protozoa.

Hepatitis B↗
PubMed2004

Identification of an expressed gene in Dipylidium caninum.

Recombinant DNA studies have been focused on developing vaccines to different cestodes. But few studies involving Dipylidium caninum molecular biology and genes have been done. Only partial sequences of mitochondrial DNA and ribosomal RNA gene are available in databases. Any molecular work with this parasite, including epidemiology, study of drug-resistant strains, and vaccine development, is hampered by the lack of knowledge of its genome. Thus, the knowledge of specific genes of different developmental stages of D. caninum is crucial to locate potential targets to be used as candidates to develop a vaccine and/or new drugs against this parasite. Here we report, for the first time, the sequencing of a fragment of a D. caninum expressed gene.

Animals↗
PubMedDate not supplied

Why certain vaccines have been delayed or not developed at all.

Vaccine development is a long process, with the time from early research to licensure steadily increasing. At one time the process took about ten years; now it takes closer to fifteen to twenty years. The process begins with investigators in universities or biotech firms who have an idea. However, to take things further, there must be a vaccine manufacturer, a regulatory authority ready to give permission for the use of the vaccine, and public health authorities that will recommend and foster vaccination.

Developing Countries↗
PubMed1998

Development of new vaccines for tuberculosis. Recommendations of the Advisory Council for the Elimination of Tuberculosis (ACET).

Tuberculosis (TB) remains a major, global public health problem, particularly in low-income countries. Better application of current diagnostic, treatment, and prevention strategies could lead to gradual decreases in the disease, but eliminating TB completely in the United States and internationally will require new tools. The greatest impact could come from a new vaccine, and recent technological advances have provided the basis for new vaccine development. However, sustained support is required to move the research from the laboratory to field trials of vaccines and to implement new vaccine programs. Recognizing the importance of TB vaccines, the Advisory Council for the Elimination of Tuberculosis (ACET) recommends that public agencies and vaccine manufacturers develop a comprehensive, consensual strategy to achieve these goals. This report outlines the elements that should be considered in devising a strategic plan for vaccine development.

Bacterial Vaccines↗
PubMed1992

Multiple discontinuity as a remarkable feature of the development of acellular pertussis vaccines.

Development of the Japanese acellular pertussis vaccines (APVs) of the 1980s involved six procedural or conceptual features that were discontinuous with the then-accepted views of how pertussis vaccines should be made and tested. These discontinuities were: modification of the standard intracerebral mouse test for protective potency; use of culture supernates, rather than cells, of Bordetella pertussis as the feedstock for antigen purification; use of haemagglutination as a measure of protective antigen(s); identification of pertussis toxin (PT) as the main protective antigen; complete inactivation of the biological activities of PT by formalin; and the use of a single strain of B. pertussis. Several of these discontinuities had long precedence in the pertussis literature, but the original observations had not been incorporated into the mainstream of pertussis vaccinology and were therefore 'premature'. The APVs, purified from culture-supernates, emerged after a long period of unsuccessful research on the split-cell pertussis vaccines, i.e. those derived from the bacterial cells themselves. There is a brief discussion of why APVs have taken so long to obtain acceptance outside Japan, and of how the listed discontinuities may be explicable in terms of antigen processing by the immune system. General lessions, applicable to vaccines for other infectious diseases, may be learned from this account of how APVs have evolved from whole-cell pertussis vaccines.

Animals↗
PubMed2004

Regulatory pathways for vaccines for developing countries.

Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world.

Developing Countries↗
PubMedDate not supplied

[BCG vaccination and development of an innovative vaccine for preventing vertical HIV transmission in Africa].

"Families First Africa" is an international project whose main objective is to develop a pediatric vaccine that protects infants against HIV transmission during breast feeding. The vaccine being developed consists of HIV peptides matching HLA genotypes of the Western Africa population and will be administered in association with BCG vaccine which acts as a strong adjuvant. An alternative strategy is to administer a recombinant BCG vaccine with HIV gene fragments which codify for the same peptides.

AIDS Vaccines↗
PubMed2001

Mucosal immunization with HIV-1 gag DNA on cationic microparticles prolongs gene expression and enhances local and systemic immunity.

There is an urgent need to develop vaccines against transmission of HIV through the vaginal and rectal mucosa. In the present study we tested the ability of DNA encoding HIV-1 gag adsorbed onto the surface of cationic polylactide co-glycolide microparticles (PLG-DNA) to induce local and systemic gag-specific immunity following mucosal delivery. We found gag-specific cell- and antibody-mediated responses in local as well as systemic lymphoid tissues following intranasal (IN) immunizations with PLG-DNA but not with naked DNA. IN immunizations with PLG-DNA, but not naked DNA, induced prolonged expression of gag protein in local and systemic lymphoid tissues. These data have important implications for DNA vaccine development.

AIDS Vaccines↗