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1.
Eliane Namie Miyaji Maria Leonor Sarno Oliveira Eneas Carvalho Paulo Lee Ho 《Cellular and molecular life sciences : CMLS》2013,70(18):3303-3326
Streptococcus pneumoniae remains an important cause of disease with high mortality and morbidity, especially in children and in the elderly. The widespread use of the polysaccharide conjugate vaccines in some countries has led to a significant decrease in invasive disease caused by vaccine serotypes, but an increase in disease caused by non-vaccine serotypes has impacted on the overall efficacy of these vaccines on pneumococcal disease. The obvious solution to overcome such shortcomings would be the development of new formulations that provide serotype-independent immunity. This review focuses on the most promising approaches, including protein antigens, whole cell pneumococcal vaccines, and recombinant bacteria expressing pneumococcal antigens. The protective capacity of these vaccine candidates against the different stages of pneumococcal infection, including colonization, mucosal disease, and invasive disease in animal models is reviewed. Some of the human trials that have already been performed or that are currently ongoing are presented. Finally, the feasibility and the possible shortcomings of these candidates in relation to an ideal vaccine against pneumococcal infections are discussed. 相似文献
2.
D W Taylor 《Experientia》1991,47(2):152-157
Schistosomiasis control currently relies primarily on chemotherapy which is both expensive and temporary. There is an urgent need for an effective vaccine. Studies in animal models and man have demonstrated the existence of protective immunity. Antibody-dependent cell-mediated cytotoxicity mechanisms involving eosinophils and macrophages have been implemented in destruction of the parasites. Antigens expressed on the surface of the schistosomulum are among the targets of protective immune responses. Vaccines comprising recombinant antigens are now being tested in vivo for their capacity to evoke protective responses. Live oral vaccines based on attenuated Salmonella expressing schistosomular surface antigens are being developed. 相似文献
3.
S J Cryz 《Experientia》1991,47(2):146-151
Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages of Plasmodium and Schistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed. 相似文献
4.
Good MF 《Cellular and molecular life sciences : CMLS》2011,68(7):1105-1113
Malaria presents a challenge to world health that to date has been beyond the abilities of researchers to conquer. This critique
presents some of the strategies employed by the parasite to overcome immunity and the immunological challenges that we face
to develop vaccines. A conclusion is that a vaccine must identify novel antigens or epitopes that are not normally immunogenic
and which are therefore not under immune pressure and most likely to be conserved between different strains. Such antigens
are most likely to be targets of cellular immunity. The case for a whole parasite blood stage vaccine is presented based on
these premises. 相似文献
5.
Flock House virus (FHV) is a nonenveloped, icosahedral insect virus whose genome consists of two molecules of single-stranded, positive-sense RNA. FHV is a highly tractable system for studies on a variety of basic aspects of RNA virology. In this review, recent studies on the replication of FHV genomic and subgenomic RNA are discussed, including a landmark study on the ultrastructure and molecular organization of FHV replication complexes. In addition, we show how research on FHV B2, a potent suppressor of RNA silencing, resulted in significant insights into antiviral immunity in insects. We also explain how the specific packaging of the bipartite genome of this virus is not only controlled by specific RNA-protein interactions but also by coupling between RNA replication and genome recognition. Finally, applications for FHV as an epitopepresenting system are described with particular reference to its recent use for the development of a novel anthrax antitoxin and vaccine. 相似文献
6.
Towards progress on DNA vaccines for cancer 总被引:2,自引:0,他引:2
Lowe DB Shearer MH Jumper CA Kennedy RC 《Cellular and molecular life sciences : CMLS》2007,64(18):2391-2403
Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived
immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA
represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response
in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed
well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not
impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing
DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid
DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response
while also targeting tumor evasion mechanisms.
Received 2 April 2007; received after revision 14 May 2007; accepted 21 May 2007 相似文献
7.
S. J. Cryz Jr 《Cellular and molecular life sciences : CMLS》1991,47(2):146-151
Summary Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages ofPlasmodium andSchistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed. 相似文献
8.
Bleifuss E Kammertoens T Hutloff A Quarcoo D Dorner M Straub P Uckert W Hildt E 《Cellular and molecular life sciences : CMLS》2006,63(5):627-635
Cell-penetrating peptides (CPPs) have been shown to improve antigen loading of dendritic cell vaccines. Here we asked whether
fusion of a CPP to a protein improves its immunogenicity when this fusion protein is directly applied as vaccine. We used
the cell-penetrating translocation motif (TLM) derived from the hepatitis B virus, because no size limitation of cargos has
been observed. Increased immunogenicity was observed when TLM was fused to ovalbumin (TLM-ova). TLM-ova was found to be superior
to ova in inducing proliferation and cytotoxicity of ova-specific CD8+ T cells in vitro and in vivo. Using ovalbumin-expressing thymoma cells (EG7-ova), an improved anti-tumor immune response was observed for TLM-ova vaccination
versus vaccination with ova. Moreover, TLM-ova vaccination induced a higher titer of anti-ovalbumin IgG2a antibodies compared
to ova. These data demonstrate that CPP-protein vaccines can improve cellular as well as humoral immune responses.
Received 16 November 2005; received after revision 12 December 2005; accepted 10 January 2006
†These authors contributed equally to this work 相似文献
9.
Anthrax toxins 总被引:3,自引:0,他引:3
Though its lethal effects were ascribed to an exotoxin almost half a century ago, the pathogenesis of anthrax has yet to
be satisfactorily explained. Subsequent work has led to the molecular identification and enzymatic characterization of three
proteins that constitute two anthrax toxins. Protective antigen binds an as yet unknown cell receptor and mediates the entry
of the other two components to the cytoplasm via the endosomal pathway. Edema factor, so named for its ability to induce edema,
is a Ca2+/calmodulin-dependent adenylate cyclase. Lethal factor, the dominant virulence factor associated with the toxin, proteolytically
inactivates mitogen-activated protein kinase kinases, key players in signal transduction. We describe the fascinating work
that has led to these discoveries and discuss their relevance to our understanding of the pathogenesis of anthrax.
Received 6 January 1999; received after revision 8 March 1999; accepted 9 March 1999 相似文献
10.
J.A. Wilson C.M. Bosio M.K. Hart 《Cellular and molecular life sciences : CMLS》2001,58(12-13):1826-1841
Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection. 相似文献
11.
Schistosome vaccines 总被引:2,自引:0,他引:2
D. W. Taylor 《Cellular and molecular life sciences : CMLS》1991,47(2):152-157
Summary Schistosomiasis control currently relies primarily on chemotherapy which is both expensive and temporary. There is an urgent need for an effective vaccine. Studies in animal models and man have demonstrated the existence of protective immunity. Antibody-dependent cell-mediated cytotoxicity mechanisms involving eosinophils and macrophages have been implemented in destruction of the parasites. Antigens expressed on the surface of the schistosomulum are among the targets of protective immune responses. Vaccines comprising recombinant antigens are now being tested in vivo for their capacity to evoke protective responses. Live oral vaccines based on attenuatedSalmonella expressing schistosomular surface antigens are being developed. 相似文献
12.
Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant 总被引:2,自引:0,他引:2
The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces
the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic
immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl
lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like
receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned
about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak
version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions
needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects.
Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008 相似文献
13.
White MD Bosio CM Duplantis BN Nano FE 《Cellular and molecular life sciences : CMLS》2011,68(18):3019-3031
Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive
(TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are
cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss the distribution of temperature
in the human body, and relate how the temperature differential can be exploited for designing and using TS vaccines. We also
examine how one of the coolest organs of the body, the skin, contains antigen-processing cells that can be targeted to provoke
the desired immune response from a TS vaccine. We describe traditional approaches to making TS vaccines, and highlight new
information and technologies that are being used to create a new generation of engineered TS vaccines. We pay particular attention
to the recently described technology of substituting essential genes from Arctic bacteria for their homologues in mammalian
pathogens as a way of creating TS vaccines. 相似文献
14.
Botulinum toxin as a carrier for oral vaccines 总被引:1,自引:0,他引:1
Simpson LL Maksymowych AB Kiyatkin N 《Cellular and molecular life sciences : CMLS》1999,56(1-2):47-61
Botulinum toxin is an unusually potent substance that acts on the nervous system to produce the clinical outcome of flaccid
paralysis. To produce this effect, the toxin ordinarily proceeds through two separate but essential sequences of events. During
the first, the toxin is ingested, it traverses a portion of the gastrointestinal system and then it is transcytosed from the
lumen of the gut to the general circulation. During the second, circulating toxin binds to peripheral cholinergic nerve endings,
it is endocytosed and then it acts as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. Although
botulinum toxin is antigenic, it ordinarily does not evoke an immune response during or after cases of oral poisoning. This
is due to the fact that the dose of toxin that produces flaccid paralysis—and potentially death—is less than the dose needed
to evoke an antibody response. In the recent past, the techniques of molecular biology have been used to generate an expression
product of botulinum toxin that retains the ability to escape the gut and reach the general circulation, retains the ability
to evoke an immune response, but has lost the ability to produce neurotoxicity. This modified toxin may have two clinical
applications. The expression product itself may have utility as an oral vaccine against botulism. Beyond this, the modified
toxin, or a truncation mutant of the toxin, may have utility as a carrier in the construction of other oral vaccines. Both
potential applications could lead to the expression of oral vaccines in common foods.
Received 29 December 1998; received after revision 22 March 1999; accepted 24 March 1999 相似文献
15.
Immune responses to DNA vaccines 总被引:16,自引:0,他引:16
DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce
protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed
efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a
full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA
vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore,
the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants
or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines
invites their use not only as vaccines but also as research tools for immunologists and microbiologists.
Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998 相似文献
16.
Ludivine A. Pradelli Marie Bénéteau Jean-Ehrland Ricci 《Cellular and molecular life sciences : CMLS》2010,67(10):1589-1597
Mitochondria control whether a cell lives or dies. The role mitochondria play in deciding the fate of a cell was first identified
in the mid-1990s, because mitochondria-enriched fractions were found to be necessary for activation of death proteases, the
caspases, in a cell-free model of apoptotic cell death. Mitochondrial involvement in apoptosis was subsequently shown to be
regulated by Bcl-2, a protein that was known to contribute to cancer in specific circumstances. The important role of mitochondria
in promoting caspase activation has therefore been a major focus of apoptosis research; however, it is also clear that mitochondria
contribute to cell death by caspase-independent mechanisms. In this review, we will highlight recent findings and discuss
the mechanism underlying the mitochondrial control of apoptosis and caspase-independent cell death. 相似文献
17.
Macrophages play an essential role in the immune system by ingesting and degrading invading pathogens, initiating an inflammatory response and instructing adaptive immune cells, and resolving inflammation to restore homeostasis. More interesting is the fact that some bacteria have evolved to use macrophages as a natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of humanity’s most successful pathogens and is the causal agent of tuberculosis, while NTMs cause opportunistic infections all of which are of significant public health concern. Here, we describe mechanisms by which intracellular pathogens, with an emphasis on mycobacteria, manipulate macrophage functions to circumvent killing and live inside these cells even under considerable immunological pressure. Such macrophage functions include the selective evasion or engagement of pattern recognition receptors, production of cytokines, reactive oxygen and nitrogen species, phagosome maturation, as well as other killing mechanisms like autophagy and cell death. A clear understanding of host responses elicited by a specific pathogen and strategies employed by the microbe to evade or exploit these is of significant importance for the development of effective vaccines and targeted immunotherapy against persistent intracellular infections like tuberculosis. 相似文献
18.
Deboer T 《Cellular and molecular life sciences : CMLS》2007,64(10):1227-1235
Sleep is investigated in many different ways, many different species and under many different circumstances. Modern sleep
research is a multidisciplinary venture. Therefore, this review cannot give a complete overview of all techniques used in
sleep research and sleep medicine. What it will try to do is to give an overview of widely applied techniques and exciting
new developments. Electroencephalography has been the backbone of sleep research and sleep medicine since its first application
in the 1930s. The electroencephalogram is still used but now combined with many different techniques monitoring body and brain
temperature, changes in brain and blood chemistry, or changes in brain functioning. Animal research has been very important
for progress in sleep research and sleep medicine. It provides opportunities to investigate the sleeping brain in ways not
possible in healthy volunteers. Progress in genomics has brought new insights in sleep regulation, the best example being
the discovery of hypocretin/orexin deficiency as the cause of narcolepsy. Gene manipulation holds great promise for the future
since it is possible not only to investigate the functions of different genes under normal conditions, but also to mimic human
pathology in much greater detail. 相似文献
19.
Summary Experiments have been carried out with strains ofBacillus anthracis andBacillus mesentericus which in consequence of a mutation have lost their capsulas.Non-capsulated living anthrax bacilli mixed with bacteria-free extracts of capsulated mesentericus bacilli may undergo a mutation which results in the appearance of constant strains of capsulated and flagellated bacilli with colony formation peculiar toBacillus mesentericus. Similarly, after treatment of non-capsulated mesentericus bacilli with extracts of capsulated anthrax bacilli it is possible to isolate capsulated mesentericus bacilli.It is pointed out that in both cases there is the question of the result of an induced mutation caused by the introduction of genes of the one species into the other. 相似文献
20.
Huib J. Zuidervaart 《Annals of science》2016,73(3):257-288
This paper discusses the scientific instruments made and used by the microscopist Antony van Leeuwenhoek (1632–1723). The immediate cause of our study was the discovery of an overlooked document from the Delft archive: an inventory of the possessions that were left in 1745 after the death of Leeuwenhoek's daughter Maria. This list sums up which tools and scientific instruments Leeuwenhoek possessed at the end of his life, including his famous microscopes. This information, combined with the results of earlier historical research, gives us new insights about the way Leeuwenhoek began his lens grinding and how eventually he made his best lenses. It also teaches us more about Leeuwenhoek's work as a surveyor and a wine gauger.
A further investigation of the 1747 sale of Leeuwenhoek's 531 single lens microscopes has not only led us to the identification of nearly all buyers, but also has provided us with some explanation about why only a dozen of this large number of microscopes has survived. 相似文献