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At least 343 records · Page 19Linked to original sources
PubMed2006

[Adjuvants--essential components of new generation vaccines].

Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer).

Adjuvants, Immunologic↗
PubMedDate not supplied

[Antigenic activity of measles immunostimulating complex].

The liposomal technology for preparing the immunostimulating complex (ISCOM) helped obtain a complex measles preparation whose antigens are represented by the structural proteins of measles virus in the bilayer phosphate-lipid membrane. Immunization of mice with the resultant preparation induced antimeasles antibodies with the maximum titer of antihemagglutinins 1:640 and of antihemolysins 1:1280. The biological activity of antibodies was confirmed in the neutralization test.

Animals↗
PubMed2003

The role of dendritic cells in regulating mucosal immunity and tolerance.

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and a breakdown in this homeostatic process can lead to diseases such as coeliac disease or Crohn's disease. The nature ofthe intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DCs). Both oral tolerance and priming are influenced by the numbers and activation status of DCs in the gut and its draining lymphoid tissues, and our current work indicates that dietary proteins are taken up preferentially by DCs in the lamina propria of the small intestine. These then migrate to interact with antigen-specific CD4+ T cells in the mesenteric lymph node. In vivo and in vitro studies using purified lamina propria DCs suggest these may play a unique role in the regulation of intestinal immune responses. We propose that local DCs are the gatekeepers of the mucosal immune system, inducing tolerance under physiological conditions, but being sufficiently responsive to inflammatory stimuli to allow T cell priming and protective immunity when necessary. In addition, we will discuss evidence that adjuvant vectors such as ISCOMS may be effective mucosal vaccines due to an ability to activate intestinal DCs.

Animals↗
PubMed1989

Analysis of the feline immune response to human myelin-associated glycoprotein.

Elucidation of the pathogenesis of demyelinating peripheral neuropathy associated with myelin-associated glycoprotein (MAG) binding IgM paraproteins requires an in vivo animal model of the syndrome. Multiple immunizations of cats with MAG in Freund's adjuvant did not produce an antibody response but four immunizations with MAG-iscom (Morein, B. et al. (1984) Nature, 308: 457-460) did induce IgM antibodies which bound to human MAG and cat peripheral nerve myelin. Despite the presence of antibody for a 13-month period, no neuropathy developed. At necropsy, the peripheral nerves were ultrastructurally normal and no antibody was detectable in the endoneurium. A competitive ELISA indicated that the cat and human IgM antibodies recognized different epitopes.

Animals↗
PubMed1993

Local antibody forming cell responses to the Hitchner B1 and Ulster strains of Newcastle disease virus.

The Hitchner B1 and Ulster strains of Newcastle disease virus (NDV) replicated to high titre in the Harderian gland (HG) after eye-drop infection. The Harderian gland then became the major site of antiviral IgA-antibody-forming cells (AFC) in the body and their number correlated to the level of antiviral IgA antibody in the tears. The spleen, HG and femoral bone marrow all contained comparable levels of antiviral IgG-AFC and IgM-AFC after two intra-ocular inoculations of virus, whereas the caecal tonsil and bursa contained few AFC despite the local replication of the Ulster strain of NDV leading to high titres of virus in the faeces. Vaccines of the Hitchner B1 strain of NDV were much less effective at inducing antibody by the intranasal compared with intra-ocular route and no virus was re-isolated after intranasal vaccination. The intravenous inoculation of inactivated Iscoms of NDV could stimulate the spleen, but not the Harderian gland to the same extent as a live virus.

Animals↗
PubMed1991

Immunoaffinity purification of two major proteins of bovine leukemia virus (gp51 and p24) and their use for discrimination between vaccinated and infected animals.

The outer envelope glycoprotein gp51 and the core protein p24 of bovine leukemia virus (BLV), were purified from culture media of FLK-BLV cells by a single-step procedure, using immunoaffinity chromatography based on monoclonal antibodies to the respective proteins. About 90% of the envelope glycoprotein in the culture medium was recovered as a highly purified product. Both purified protein (gp51 and p24) preparations, were found to be highly specific antigens by ELISA, and did not cross-react with sera raised against the other antigen. The conformational epitopes on the purified gp51 were preserved as judged by their reactions with the corresponding monoclonal antibodies. The p24 ELISA reacted only with sera from naturally infected animals and not with sera from animals immunized with an experimental gp51-iscom vaccine. The p24 antigen is therefore useful for discriminating between BLV-infected animals and those immunized with a gp51 subunit vaccine.

Animals↗
PubMed1992

A sensitive assay for detection and measurement of neutralising antibody to human immunodeficiency virus.

An assay based on the inhibition of syncytium formation in C8166 cells was developed to measure low levels of neutralising antibody (NT-AB) to human immunodeficiency virus (HIV) and to detect cross-reactivity between virus strains. The relationship between virus challenge and antibody titre was represented by a tripartite curve which was essentially linear over moderate levels of virus input. Based on these findings, antibody titres were standardised against 100 TCID50 of challenge virus. However, lower virus inocula were found to detect minimum levels of antibody. Reproducibility of antibody titres between tests was high, with variation generally lying within one dilution step. The improved sensitivity of the technique allowed detection of NT-ABs in animals immunised with immune-stimulating complexes (ISCOMS) incorporating HIV antigens. Consistent levels of cross-reactivity between HIV strains was demonstrated, indicating the presence of distinct viral groups, from which dominant isolates may be chosen for use in vaccination studies.

Animals↗
PubMed1994

T-cell adjuvants.

T-cell adjuvancy involves the use of agents to stimulate preferentially delayed type hypersensitivity (DTH). Traditional adjuvants like Alum, Freunds, muramyl peptides, and endotoxins are not selective. Natural infection (e.g. vaccinia) may yield selective DTH. Low dose cyclophosphamide (CY) with mycobacteria was the first experimental T-cell adjuvant. New adjuvant formulations (ISCOMS, MAPS, etc.) with synthetic T-cell epitopes offer improved formulations. Upregulation of TH-1 helper cells and their actions with interleukins like IL-2, IL-12, and gamma IFN or antibodies to IL-4 and IL-10 may augment potently pathogen and tumor resistance. Similarly, transfection of tumor target cells with genes for IL-2, IL-12, gamma IFN, etc., offers novel vaccine treatment approaches. Finally, "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH responses. These approaches are seeing increasing emphasis in new treatment strategies for cancer and infections like HIV.

AIDS Vaccines↗
PubMed1990

Vaccination of Balb/c mice against enteroviral mediated myocarditis.

A non-virulent strain of Coxsackie B3 (CB3) virus was used to produce a subunit vaccine. It contains the capsid proteins VP1, 2, 3 and probably 4 and can be made RNA-free. It is based on the ISCOM technology ensuring non-toxic properties and good adjuvant effect. Vaccinated animals at doses above 16 ng were completely protected from mortality when challenged with a myocarditic strain of CB3. Histologically no inflammatory lesions were found in the heart. This was corroborated using immune histological techniques with monoclonal antibodies against lymphocyte subsets. Even at a dose of 0.16 ng a delayed mortality was observed. Neutralizing antibody titres rose to 512, thus ensuring a circulating level well above that considered protective. It is suggested that vaccination might be a possible way of prophylaxis for myocarditis and even dilated cardiomyopathy, the latter presently being the chief cause of heart transplantation. By persistence or triggering of autoimmune phenomena Coxsackie virus is incriminated as the first step in pathogenesis.

Animals↗
PubMed1995

Adjuvants for human vaccines--current status, problems and future prospects.

Adjuvants help antigen to elicit an early, high and long-lasting immune response with less antigen, thus saving on vaccine production costs. In recent years, adjuvants received much attention because of the development of purified, subunit and synthetic vaccines which are poor immunogens and require adjuvants to evoke the immune response. With the use of adjuvants immune response can be selectively modulated to major histocompatibility complex (MHC) class I or MHC class II and Th1 or Th2 type, which is very important for protection against diseases caused by intracellular pathogens such as viruses, parasites and bacteria (Mycobacterium). A number of problems are encountered in the development and use of adjuvants for human vaccines. The biggest issue with the use of adjuvants for human vaccines, particularly routine childhood vaccines, is the toxicity and adverse side-effects of most of the adjuvant formulations. At present the choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable low level of side-effects. Other problems with the development of adjuvants include restricted adjuvanticity of certain formulations to a few antigens, use of aluminum adjuvants as reference adjuvant preparations under suboptimal conditions, non-availability of reliable animal models, use of non-standard assays and biological differences between animal models and humans leading to the failure of promising formulations to show adjuvanticity in clinical trials. The most common adjuvants for human use today are still aluminum hydroxide and aluminum phosphate, although calcium phosphate and oil emulsions also have some use in human vaccinations. During the last 15 years much progress has been made on development, isolation and chemical synthesis of alternative adjuvants such as derivatives of muramyl dipeptide, monophosphoryl lipid A, liposomes, QS21, MF-59 and immunostimulating complexes (ISCOMS). Other areas in adjuvant research which have received much attention are the controlled release of vaccine antigens using biodegradable polymer microspheres and reciprocal enhanced immunogenicity of protein-polysaccharide conjugates. Biodegradable polymer microspheres are being evaluated for targeting antigens on mucosal surfaces and for controlled release of vaccines with an aim to reduce the number of doses required for primary immunization. Reciprocal enhanced immunogenicity of protein-polysaccharide conjugates will be useful for the development of combination vaccines.

Adjuvants, Immunologic↗
PubMed1995

Antigenicity and immunogenicity of recombinant envelope glycoproteins of SIVmac32H with different in vivo passage histories.

Shortly after infection of two rhesus monkeys (Macaca mulatta) either with a SIVmac32H challenge stock or with the same virus that had been passaged in another rhesus monkey for 11 months, SIV-envelope genes were cloned from their peripheral blood mononuclear cells and subsequently expressed by recombinant vaccinia viruses. The molecular weights and antigenicities of the thus produced envelope glycoproteins were largely identical to those of the native SIV. The envelope glycoprotein derived from the in vivo passaged virus proved to be poorly recognized by virus neutralizing monoclonal antibodies directed against one of the seven antigenic sites for which monoclonal antibodies were available. Immunization studies in rats showed that this protein was also less efficient in inducing antibodies against this antigenic site, and that it induced significantly lower levels of virus neutralizing antibodies than the other SIV-envelope glycoprotein. The immunogenicity of the SIV-envelope glycoprotein incorporated into immune stimulating complexes (iscoms) was compared to that of the same protein presented with Quil A or MDP-tsl.

Amino Acid Sequence↗
PubMed1995

Stimulation of rotavirus IgA, IgG and neutralising antibodies in baboon milk by parenteral vaccination.

A rhesus rotavirus vaccine adjuvanted with ISCOMs was injected intramuscularly to 5 pregnant baboons, with repeated doses 1-2 and 14 weeks after delivery. Maternal blood and milk samples and blood samples from their babies were collected at 2-weekly intervals until 26 weeks after parturition. Samples were assayed for rotavirus antibodies by ELISAs and neutralisation tests. Vaccination produced statistically significant increases in maternal serum IgG and neutralising antibodies, and in milk IgA, IgG, and neutralising antibodies. Control baboon mothers sampled from 12 weeks after delivery had lower serum and milk antibody titres, but responded to vaccination at 16 weeks by producing a similar antibody profile in serum and milk to those previously vaccinated. Because of the endemic nature of human rotaviral infections, similar maternal vaccinations have potential as a means of increasing milk antibodies to a level at which they may be protective to infants.

Animals↗
PubMed1995

The influence of adjuvants on oral vaccination of chickens against Newcastle disease.

Living V4 strain Newcastle disease vaccine was given to chickens orally. The inclusion of DEAE-dextran, Quil-A or TiterMax in the vaccine, or delivering the vaccine as Iscoms, did not enhance the serological response. The immediate serological response to living V4 vaccine was enhanced in the presence of Avridine. Chickens produced a low serological response to oral administration of inactivated V4 vaccine. This response was not enhanced in the presence of Avridine.

Adjuvants, Immunologic↗
PubMed2004

Identification of adjuvants that enhance the therapeutic antibody response to host IgE.

In the development of a novel vaccine against atopic allergies, we have screened for adjuvants that enhance the therapeutic antibody response against self immunoglobulin E (IgE). The response against self IgE is induced by administration of a vaccine antigen, which contains both self and non-self IgE regions, together with an adjuvant. We evaluated five commonly used adjuvants; Freund's, aluminium hydroxide, ISCOMs, Montanide ISA 51 and Montanide ISA 720, and found that the mineral oil-based adjuvants; Montanide ISA 51 and Freund's induced at least 5-10-fold higher anti-self IgE titers than any of the other candidates. However, with one exception, Alum, the immune responses against the carrier, i.e. the non-self regions, were similar for all adjuvants, indicating that the ability to induce responses against self and non-self antigens differ among adjuvants. The responses against non-self IgE were more than 50-fold higher than antibody responses against self IgE in both the Freund's and Montanide 51-administered animals, indicating that the response against self molecules is markedly inhibited by tolerance-inducing mechanisms. Co-administration of Montanide ISA 51 with immuno-stimulatory substances from bacteria; muramyldipeptide (MDP), monophosphoryl-lipid A (MPL) or a formyl-methionine-containing tripeptide (fMLP), did not elevate the anti-self IgE response. Hence, adjuvants based on pure mineral oil without additional immuno-stimulatory substances appear to be the best adjuvant candidates in therapeutic vaccines aimed at regulating the in vivo levels of self-proteins.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2005

Purification of phocid herpesvirus type 1 glycoproteins B and D and pilot studies of immunogenicity in mice.

In the process of developing a subunit vaccine against phocid herpesvirus type 1, we have cloned and expressed the glycoproteins B and D (gB and gD) of phicid herpesvirus type 1, using an eukaryotic baculovirus expression system. To establish the proof of concept, candidate iscom vaccines based on these affinity-purified proteins either alone or in combination, were tested for their immunogenicity in BALB/C mice. Mice immunised with a combination of gB and gD developed higher antibody and proliferative T cell responses against PhHV-1 than those immunised with gB or gD alone. The corresponding antibody and T cell proliferative responses were higher against PhHV-1 than against FHV. These data favour further testing of these candidate vaccines based on gB and gD in the FHV-cat model.

Animals↗
PubMed2006

Adjuvants: present regulatory challenges.

Research on new adjuvants and delivery systems has expanded dramatically in the last decade. New generation vaccines, based on recombinant proteins, synthetics, and conjugated antigens have emerged but they have limitations because of their poor immunogenic properties, and therefore more cooperative adjuvants for the promotion of the immune response are required. Different molecules have been screened for their ability to enhance the immune response to vaccine antigens, e.g. liposomes, protein cochleate formulations, ISCOMs and cytokines, to name the few. However, most of the vaccines that are currently licensed use aluminum salts or calcium phosphate.

Adjuvants, Immunologic↗
PubMed2005

IgG avidity pattern in cattle after ingestion of Neospora caninum oocysts.

The avidity (functional affinity) of specific antibodies are being used to estimate duration of bovine Neospora caninum infection. Here, we report for the first time the avidity pattern in cattle orally inoculated with N. caninum oocysts. In all, 16 pregnant cows and 7 calves were administered N. caninum oocysts. In the cows, the avidity increased during the early course of infection. In all but one, the avidity was < or = 35 during the first 6 weeks after infection and no cow had an avidity value >50 until week 9. The calves were sampled either week 6 (n = 3) or week 9 (n = 9) after infection, and by then had avidities between 2 and 17. The results are in agreement with results from previous investigations of naturally infected cattle, and calves that were experimentally infected with tachyzoites. They further validate the ability of the N. caninum iscom avidity ELISA to accurately assess the duration of infection.

Animals↗
PubMed2006

Application of repeated bulk milk testing for identification of infection dynamics of Neospora caninum in Thai dairy herds.

In this prospective study, repeated bulk milk tests were evaluated to establish the Neospora caninum antibody status and to describe infection dynamics and changes in prevalence of N. caninum in Thai dairy herds. Bulk milk from 418 herds in northeast Thailand were collected at three consecutive samplings, in December 2002 (sampling 1), April (sampling 2) and December 2003 (sampling 3). All samples were analysed for presence of N. caninum antibodies by iscom ELISA, and the optical density values were dichotomized at three different cut-offs. Herd status at either sampling 1 or sampling 2 was used to predict herd status at sampling 3. Changes in both sensitivity and specificity at the first samplings at all cut-offs were consistent with commonly seen patterns when evaluating performance of diagnostic tests. In addition, the predictive positive values (PPV) of herd status at each of the two samplings were more affected by time of sampling than choice of cut-off, whereas the predictive negative values (PNV) increased with increasing cut-off. Herd status at the first samplings was also interpreted in combination, i.e. herds that were negative at both samplings were considered negative and positive otherwise in Combination A, while herds positive at both samplings were considered positive in Combination B. When using these combinations, Combination A gave higher PNV but lower PPV than Combination B at all cut-offs. Using the optical density value 0.20 as cut-off to establish the herd N. caninum antibody status, 270 herds (65%) kept their status throughout the study period, but 148 herds converted their status at least once. Interestingly, 136 (86%) of the 158 herds that were considered negative at sampling 1 and sampling 2 remained negative at sampling 3. In addition of the 159 herds considered positive at the first two samplings, 134 (84%) were still positive at sampling 3. We concluded that repeated bulk milk testing at regular intervals provided better information about herd N. caninum status than a single test. Further, our results showed that the infection is prevalent in northeast Thailand, but that a herd can keep a negative infection status despite the frequent presence of dogs.

Animals↗