Overviews of current vaccine development in respects to the idea of elaborate vaccines simple to handling and administer. The progress made recently in technologies concerning adjuvants, antigen formulation and vaccine delivery systems has been summarized. Special attention has been focused on mucosal way of vaccine application and orally induced immunity as well newest achievements in the technology using plant as vaccine carriers.
Leishmaniasis causes significant morbidity and mortality worldwide, constituting an important public health problem. Leishmania infections cause a wide spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Attempts to develop an effective vaccine to control leishmaniasis have been shown to be feasible, but no vaccine is in active clinical use. The ability to create genetically modified parasites by eliminating virulence or essential genes is considered a powerful alternative in the development of an effective protective vaccine. Here, recent findings related to genetically defined live attenuated Leishmania parasites as promising vaccine candidates are reviewed.
Bovine leukemia virus (BLV) is the causative agent for enzootic bovine lekosis (EBL). The article concerns the applications of some biotechnological achievements in the development of modern diagnostic methods, new approaches to specific prophylaxis against BLV as well as the selection of naturally resistant animals.
Gram-negative non-fermenting bacilli, particularly Pseudomonas aeruginosa and Acinetobacter spp., are important opportunistic pathogens in hospitalized patients, contributing to their morbidity and mortality. Recently, a rapid increase in frequency of multidrug-resistant clinical strains is being recorded, making the available therapeutic options very limited. Apart from the development of novel classes of antimicrobials, there is renewed interest in the use of old agents or new combinations of available drugs. Numerous in vitro investigations have been reported on the efficacy of different antimicrobials; however, they should be evaluated in experimental infection models and clinical trials. Novel approaches are being investigated, such as inhibition of virulence factor expression by pathogens or inhibition of their metabolic pathways. The use of bacteriophages, particularly those genetically modified, remains an alternative option in the therapy of infections caused by multidrug-resistant strains. Several vaccines against P. aeruginosa are under development. Apart from therapy with antimicrobial agents, eradication of outbreaks comprises implementation of strict infection control measures and prudent use of antimicrobials.
Potent but safe adjuvants are required to circumvent the many limitations of the newborn immune system to induce rapidly effective and long lasting immunity to subunit vaccines. By the use of pattern recognition receptors, antigen-presenting cells (APC) can very efficiently be activated by ?danger? motifs expressed by various pathogens. APC activated by ?danger? motifs, such as immunostimulatory sequences of bacterial DNA, can not only transmit the activation signal from the innate immunity to the adaptive compartment, but also shape the antigen-specific immune responses. Molecules or compounds expressing ?danger? motifs could, therefore, be considered for use as adjuvants for subunit vaccines. In this review, the authors discuss the promises and potential drawbacks that such novel adjuvants could hold for their use in experimental and clinical early life vaccinations.
Bivine herpervirus 1 (BHV 1) called also IBR/IPV virus is a member of the Herpersviridae family, Alphaherpersviridae subfsmily.The BHV 1 virus is an important pathogen of cattle, widely spread in the world.It is responsible for various diseases like infractious bovine rhinotracheitis (IBR), pustular vulvovaginitis (IPV), encephalitis, conjunctivitis, mastitis, enteritis and abortion.Four clinical forms of BHV 1 infections have been confirmed in Poland.THe paper summarized the research review on genome organization and function of the essential BHV 1 protein, BHV 1 genome is composed of a unique long segment UL anda unique short segment Us flanked by inverted repeats IRS and TRS.THe genome codes for 28-35 major envelope proteins among which gB, gC and gD play an important role in virus attachement and penetration into cells.Glycoprotein gD plays a crucial role in the stimulation of immune response and antibodies against gD, neutralizing virus infectivity.
Tuberculosis (TB) remains a global health problem. There is an intense effort to identify correlates of protective immunity and to design new TB vaccines. CD8 T cells are thought to play a significant role in controlling Mycobacterium tuberculosis infection. Relatively little has been published about the antigens and epitopes targeted by mycobacteria-specific CD8 T cells. Here we present an update of our 1999 overview of human CD8 T cell epitopes in mycobacterial antigens and discuss related issues relevant to TB diagnosis and vaccine development.
Both vaccines ware safe and immunogenic when administered in foxes and minks.Among the inactivated vaccines, the MEV-143 virus inactivated with betha-priopiolactone demonstrated best antigenic properties.The level of antibodies in the sera of immunized animals was equal to antibody titre induced by attenuated virus of polish vaccine Faxvac Parwo or reference vaccines Biovac D and Nordent vet.
Human papillomaviruses (HPVs) are a large group, with over 100 genotypes, of small nonenveloped, double-stranded DNA viruses. HPV types may be classified by infection location on the body each virus tends to infect and its potential for oncogenesis. ?High-risk' and ?low-risk' nomenclature was proposed for HPV genotypes (HPV-HR and HPV-LR). HPV is the major etiologic factor in cervical cancer and is found in the majority of cervical tumors. The major mechanisms through which HPV contributes to neoplastic initiation and progression include the activity of two viral oncoprotein, E6 and E7, which interfere with critical cell cycle tumor suppressive proteins, p53 and pRB. However, HPV infection is not a sufficient cause of cervical cancer and other cofactors contribute to the multi-step process or tumor formation, such as individual genetic variation as well as environmental factors. Recently, prophylactic HPV vaccines have been shown to be effective in preventing infection in young women.
Fimbriae play important role as pathogenic factors in many bacteria by their adhesive properties. Adhesin is located at the tip fimbriae but also in other parts of fimbriae. Recent findings on structure of fimbriae genes and their expression for the biosynthesis and formulation of complete fimbriae have been described. Special attention was focused on the participation of fimbriae in the mechanism of pathogenesis and their specificity towards tissue receptors. Most recent studies have been performed on E. coli and Klebsiella and those data predominate in this work. Fimbriae can be used for the construction of vaccine as a proteinous carrier for haptenic carbohydrate epitopes. In conjugates fimbriae express distinct immunogenic, adjuvant and protective properties.
The three antiviral vaccines discovered in the 18th century (smallpox), 19th century (rabies), and 20th century (polio) share a common feature: none would ever be licensed today for human vaccination. Yet Jenner's smallpox vaccine led to the eradication of smallpox, Pasteur's rabies vaccine represented the first successful post-exposure treatment of people bitten by rabid animals, and polio vaccine administered since its discovery in 1950 is leading to the eradication of polio (in the years 2004-2005) from the earth. However, in the case of rabies, efforts at complete eradication are unrealistic, despite the availability of a very effective vaccine, since rabies, unlike smallpox and polio, is not limited to humans and can infect all domestic and wild mammalian species. Rabies is probably the oldest known infectious disease, yet knowledge of the virus and the disease is far from complete. For instance, the appearance of 24 cases of 'cryptic' rabies in the USA, i.e. cases not associated with any bite or scratch, with an incubation period in humans extending 6-8 years, is a puzzling phenomenon that cannot be readily explained. On the other hand, rabies is one of the few strictly neuronal infections and, as such, is an excellent model for the study of neurotropic virus distribution in the brain. Apoptosis induced by a rabies strain expressing high levels of glycoprotein spreads much more slowly through brain tissue than that induced by strains producing lower glycoprotein levels. Attenuated rabies virus constructed to express twice the normal glycoprotein levels is also an excellent antigen for induction of immune responses in the host. Foreign antigens using this vector may also produce highly immunogenic vaccines. Global Approach to Immunization. Those monitoring the spread of AIDS in many parts of the world know that cost of treatment is one of the major problems in combating the disease. Vaccines against HIV face the same problem. In general, the price of vaccines and sera is exorbitant for the afflicted population in developing countries. In addition, the dearth of syringes, the unavailability of nurses and doctors to administer multiple vaccine injections, and other factors in these countries require a drastic change in current vaccine production approaches. About 12 years ago, plants became vehicles to produce biomedical reagents. Plants can be exposed directly to a construct containing a foreign gene and Agrobacterium to create a transgenic plant that, over several generations, produces the desired product. Alternatively, plants infected with a plant virus (e.g. alfalfa mosaic virus) fused with a foreign gene can propagate the foreign antigen as the virus multiplies. Extraction of the plant virus followed by purification provides the desired biomedical product. Our use of either of these systems has led to the creation of plants producing vaccines, sera, hormones, and other biological reagents. In two clinical trials at the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan, volunteers who ingested lettuce expressing hepatitis B vaccine showed hepatitis B antibodies in their sera. In another trial carried out at the Biotechnology Foundation Laboratories in Philadelphia, volunteers ingesting a spinach-rabies vaccine showed an immunological priming effect, since only one injection of commercially available rabies vaccine significantly raised the level of rabies-specific antibodies. Vaccines against HIV gp120 and Tat have been produced in spinach, and a construct of gp120 with the CD4 receptor is now being adapted to this plant. Two types of antibodies against rabies and against colorectal cancer are being produced in tobacco and in lettuce. The suboptimal quality of the currently available anthrax vaccine prompted our efforts to produce the anthrax Protective Antigen (PA)in tobacco and lettuce. Quite clearly, plants will play a prominent role in producing a variety of biomedical reagents in the future.
Streptococcus pneumoniae (the pneumococcus) remains one of the major human pathogens and one of the most common causes of community-acquired pneumonia, otitis media, sinusitis, and meningitis. Aside from the threats posed by emerging antibiotic resistance and infection with the human immunodeficiency virus, the mortality rate among those patients with severe pneumococcal disease who receive seemingly appropriate antimicrobial chemotherapy remains unacceptably high. Because of its involvement in the pathogenesis of invasive disease, pneumolysin, one of the best-characterized virulence factors of the pneumococcus, represents not only a potential vaccine target, but also a target for adjunctive therapy to antibiotics in patients with acute pneumococcal disease. In this paper we review the cytolytic and pro-inflammatory properties of pneumolysin and their involvement in sub-version of host defenses and extra-pulmonary dissemination of the pneumococcus, as well as strategies, both immunological and pharmacological, which may counter these harmful activities of the toxin.
The development of techniques of DNA recombination in vitro is a basis for the discusion of biohazard and biosafety in laboratory experiments, technological processes and for the environment. After twenty years of experience in this field no hazardous incident was published and therefore we claim that genetic engineering is safe.However, there are different degrees of biohazard in biotechnology depending on the biological agents used, and therefore safety precautions for handling them were developed. The majority of microorganisms used in biotechnology, especially for food production, is harmless.For laboratory work with pathogenes or for their technological applications (e.g. in vaccine production) the techniques of containment are developed and introduced into the praxis. In some cases new technologies eliminate the biorisk in vaccine production: safe genetically engineered instead of pathogenes are utilized.It is necessary to state, that the biosafety problem is discussed mainly from the point of view of human needs.However, the most important question is genetic engineering and biotechnology applications for the military sector.
Exosomes are small membrane vesicles derived from late endosome. They are about 30?100 nm in diameter. The secretion of exosomes is a process in which multivesicular bodies fuse with the cell membrane, and all cells that contain multivesicular endocytic compartments could theoretically secrete exosomes. The surprising biological functions of exosomes are only slowly being unveiled, but it is already clear that they serve to remove obsolete membrane proteins and act as messages of inter-cellular communication. Exosomes derived from tumor or antigen-presenting cells have been extensively investigated. They are released into the extracellular environment and fuse with the membranes of neighboring cells, delivering membrane and cytoplasmic proteins from one cell to another. Exosomes carry immunorelevant structures which play important roles in immune response, such as MHC molecules, costimulatory molecules, heat shock proteins, and naive tumor antigens. Therefore they have been suggested as potential vaccines. Consequently, exosomes have shown considerable anti-tumor effect in several studies and are in phase I clinical trials.
There are areas of proved and succesful prophylaxis of human's virus oinfections: vacines, gammaglobulin and synthetic viral inactivators.In case of vaccine application the very important tasks concern situations of decreased immunoglogical potency and viral latency.The progress and up to now achievments according to viral vaccines which may be used in immunocompromised people are presented in the paper, as well the specificity of studies on vaccines against latent viral infections.Gammaglobulin preparations especially of commercial production, are characterized.Mechanisms of their activity, different efficiency in viral infections and problem of safety, point on the important complementary role of gammaglobulin prophylactic application.Disinfecting agents grow in importance, so the main topic presented concerns the requirements, which must be fulfilled to achieve satisfactory results in preventing virus infection.
According to the latest UNAIDS figures for 1999 there were an estimated 30. 6 million people living with HIV-1, with 16000 new HIV infections per day. The only global strategy of combating new HIV infections is to make a vaccine that is affordable to developing countries, where greater than 90% of new infections occur, and that has enough efficacy to interrupt high rates of transmission. This review critically examines: 1) important immune parameters that should be considered which will allow an understanding of preventative vaccine design and 2) the mechanisms underlying immune destruction during HIV-1 infection that will facilitate design of therapeutic vaccines. A realistic goal of a preventative vaccine is to elicit protective immune responses in vaccinees that would prevent HIV-1 from replicating extensively in the host. Components of protective immunity are thought to include neutralizing antibodies (NAB) and cytotoxic T lymphocytes (CTL). Rethinking vaccine strategies has to take into account that HIV-1 vaccines must elicit primary cellular and humoral immunity via dendritic cell and Langerhan cell priming. It is only under these conditions that boosting immunity with subsequent vaccinations will allow high enough CTL effector cells and NAB titres to impede or to prevent HIV-1 replication. Success of therapeutic vaccine strategies, has to take into consideration the pathology of persistent immune stimulation by chronic HIV-1 infection. To re-stimulate immunity and re-direct immune responses, chronic immune stimulation by HIV-1 has to be alleviated by reducing high levels of viral antigen presentation by suppressing virus with antiretroviral agents. Such treatment courses may only have to be transient, long enough for immunity to respond to an immunogenic stimulus. Short-course drug therapy may then be an affordable option for many countries already carrying a high burden of HIV-1/AIDS.
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.