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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunopotentiating activities of colloidal iron hydroxide, a novel, experimental mineral adjuvant, and of aluminium hydroxide. the licensed adjuvant for human vaccines, were compared. Our studies revealed that colloidal iron hydroxide and aluminium hydroxide behaved comparably with respect to supporting induction of an antibody response to tetanus toxoid. Furthermore, mice immunized with both, the experimental vaccine (tick-borne encephalitis virus (TBEV) antigen adsorbed to colloidal iron hydroxide) or with a commercially available TBEV vaccine (adjuvanted with aluminium hydroxide), developed long-lasting antibody responses which protected the animals from TBEV infection even one year after vaccination. The use of colloidal iron hydroxide as adjuvant had the additional advantage to reproducibly support induction of HIV-1 envelope-specific cytotoxic T lymphocytes (CTL), when used as adjuvant for a HIV-1 env-carrying recombinant fowlpox virus and being applied via the subcutaneous route. Aluminium hydroxide was much less active in this respect. Non-adjuvanted recombinant fowlpox elicited CTLs only when given intravenously or intraperitoneally, vaccination routes considered not to be suitable for routine use in humans. Further studies to evaluate the use of colloidal iron as possible alternative and/or supplement for routinely used mineral adjuvants may therefore be warranted.
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PMID:Humoral and cellular immunity induced by antigens adjuvanted with colloidal iron hydroxide. 1019 10

A phase I clinical trial with the HIV-1-derived multi-epitope polypeptide (MEP) TAB9 in the oil adjuvant Montanide ISA720 (M-ISA720) was recently performed. Although severe local reactions were reported after the second and third injections of this vaccine candidate, the first inoculation was well tolerated. In this article we evaluated a prime-boost regime consisting of one inoculation of TAB9 in M-ISA720 followed by a booster with the same antigen in aluminum hydroxide. This combination of adjuvants elicited similar antibody levels in rabbits than the traditional two-dose schedule with M-ISA720. A control group injected three times with TAB9 in aluminum hydroxide developed markedly lower antibody titers. These results showed that although oil adjuvants are better than alum for priming the immune system for antibody production against TAB9, both kinds of adjuvants can be equally effective in booster immunizations. Therefore, by using the more reactogenic oil adjuvant only for priming, we should be able to eliminate the undesirable reactions characteristic of these compounds while achieving equivalent levels of specific antibodies.
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PMID:A prime-boost regime that combines Montanide ISA720 and Alhydrogel to induce antibodies against the HIV-1 derived multiepitope polypeptide TAB9. 1041 14

Subunit vaccines generally require adjuvants to elicit immune responses, but adjuvants may alter the conformation of critical epitopes and reduce vaccine efficacy. We therefore tested an immunization strategy in which antigen is covalently coupled to aluminum oxide nanoparticles using a method that favors preservation of the native conformation. The test antigen consisted of "peptomers" (head-to-tail-linked peptide homopolymers) derived from the 4th conserved region (C4) of HIV-1 gp120 which is believed to be in an alpha-helical conformation prior to binding to CD4. Immune responses in mice to peptomer-nanoparticle conjugates were compared to responses elicited by free C4 peptide and C4 peptomers, with and without the hydrophilic adjuvant muramyl dipeptide (MDP). Highest peptomer-specific serum antibody responses were induced by peptomer-particles without MDP. Serum antibodies induced by peptomer-particles also showed highest reactivity towards recombinant, glycosylated gp120 and HIV-1 infected T cells. The results suggest that this novel vaccine approach could be useful for induction of immune responses against conformation-sensitive viral antigens without the need for additional adjuvants.
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PMID:Immunization of mice with peptomers covalently coupled to aluminum oxide nanoparticles. 1046 36

1. Outline of tuberculosis epidemiology after the World War II Tuberculosis was surprisingly highly prevalent during the World War 2nd in Japan, and it was reported that the incidence of TB was as high as 698.4 in 1951. Strong TB control program has been carried out throughout the country after the new Anti-TB Law had been enacted in 1951. TB incidence decreased with the annual reduction rate of 11% up to 1976, it was one of the highest speed of TB decrease in the world. The decrease of TB is stagnating since 1977, and the incidence is still 33.9 in 1997. 2. Causes of stagnation of TB in Japan It is estimated that the annual risk of TB infection was so high as 4% in 1945 that many of the children had been infected with TB bacilli in those days. As a result, the majority of the people aged 60 years old or more at present are already infected with TB bacilli, and more than half of the new cases is being occurred among them at present in Japan. Moreover, the life span of those already infected people is extending so remarkably that the percentage of the aged is increasing and TB incidence is stagnating in Japan. The causes of the stagnation are not the spread of HIV infection or the increase of TB among the immigrants or refugees, because both of them are not so big problems in Japan. However, more severe problems of TB epidemiology in Japan are that 1. the incidence of smear positive cases didn't decrease more than these ten years, 2. the most marked stagnation of the incidence of TB is being observed among the young aged 20 to 39, 3. the incidence of TB in big cities doesn't decrease recently and 4. group infection and nosocomial TB infection is increasing recently. The author has analyzed the factors of the stagnation of TB in Japan, and come to the conclusions that it is caused by 1. the increase of the population by 3.0%, 2. the aging of the population by 41.0%, 3. the increase of compromised host (diabetes mellitus and so on) by 19.8%, and 4. other factors by 36.3%. It was considered that the main other factor is the marked stagnation of TB infection risk mainly by socioeconomic changes such as progressed urbanization and the spread of the modern housing with aluminum sash to increase the chances of TB infection in office buildings and/or private house. 3. Present problems of TB prevention, diagnosis and treatment in Japan As BCG vaccination is so widely and so repeatedly being carried out for children that the diagnosis of TB infection is almost impossible now in Japan. Accordingly the frequency and/or risk factors of TB infection in the community are not so clear. Preventive chemotherapy is given for high risk groups in Japan, but its diagnosis may become often unreliable. New techniques such as PCR, MTD, AccuProbe, RFLP and so on are used frequently in Japan, but the consideration on the false negative results of the examinations are lacking on occasion. The results of the cohort analysis of TB treatment among all the registered cases are rather satisfactory, but it was concluded that the shortening of the duration of the hospitalization and chemotherapy is advised if compared with those of Japan and those of the other developed countries.
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PMID:[The 74th Annual Meeting Special Lecture. II. Present situation and problems of tuberculosis in Japan--its prevention, diagnosis and treatment]. 1053 82

(1R,2R,3S,4S)-4-Amino-3-hydroxy-1,2-epoxybutanes, accessible in four steps from L-aminoesters, react regio- and stereoselectively with diethyl aluminum cyanide to give (1R,2S,3S,4S)-4-amino-2,3-dihydroxynitriles. Hydrolysis yields hydroxylactones equivalent to 2,3-dihydroxy-4-aminoacids. The sequence provides a novel approach to dihydroxyethylene isosteres potentially useful for new HIV-protease inhibitors.
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PMID:Stereoselective synthesis of non symmetric dihydroxyethylene dipeptide isosteres via epoxy alcohols derived from alpha-amino acids. 1057 Nov 69

In 4 of our patients on chronic dialysis, we were intrigued by the association of hypercalcemia +/- hyperphosphatemia and normal intact PTH, with anicteric cholestasis without cytolysis. This picture occurred in 2 patients after they resumed dialysis because of a transplant rejection and in a third one after discontinuation of corticosteroids, prescribed for an idiopathic thrombocytopenia. No patient was under calcitriol, CaCO3 therapy, and their hypercalcemia persisted on a low calcium dialyzate (1.25 mmol/l). Obvious etiologies of hypercalcemia were not found: vitamin D or A intoxication, hyperparathyroidism, aluminum intoxication, hemopathy, HIV infection. The hypothesis of a granulomatous disease was made and a liver biopsy was performed showing granulomas with giant epitheloid cells. In one case foreign material (silicon ?) was present in the macrophages. Extensive investigations for sarcoidosis, tuberculosis and mycosis were negative. In 2 cases the so-called "dialysis" granulomatosis actually occurred in transplanted patients, suggesting the role of a transplantation related factor (toxic or virus). In the last case HCV seroconversion was present. In the 4 cases, corticotherapy led to the disappearance of hypercalcemia and to an increase of PTH. Our patients had the biological pattern of low bone turnover disease (hypercalcemia and normal intact PTH) and bone biopsy performed in 2 showed osteomalacia or ABD without aluminum. The association of this pattern with cholestasis should evoke liver granulomatosis, which should be confirmed by a liver biopsy and lead to a treatment by corticosteroids. The masking effect of previous corticoid therapy for transplantation should be pointed out. In 2 cases serial monitoring of plasma calcitriol showed a relation between decreasing high normal calcitriol with prednisone and normalization of calcemia, suggesting the role of inappropriate synthesis of calcitriol by the granuloma. In conclusion, liver granulomatosis should be looked for in dialysis patients on the association of unexplained hypercalcemia and normal PTH with anicteric cholestasis, and confirmed by a liver biopsy. Although still of unknown etiology, its evolution is favourable under corticotherapy.
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PMID:Liver granulomatosis is not an exceptional cause of hypercalcemia with hypoparathyroidism in dialysis patients. 1062 31

HIV can be transmitted by breastfeeding. The virus is inactivated by heating. A simple and inexpensive method has been devised by which expressed breastmilk may be pasteurised in a domestic setting. The method uses the principle of heat transfer from 450 ml of water heated to boiling point in an aluminum pot to a smaller volume of milk in a glass jar placed into the water (Pretoria Pasteurisation). The aim of this study was to test the reliability of Pretoria Pasteurisation under a range of conditions. Pretoria Pasteurisation was performed using differing starting values for each of the following parameters: volume of milk (between 50 and 150 ml); initial temperature of milk (between 37 degrees C and the ambient temperature); and ambient temperature. Each of the parameters was varied within the range indicated while all other conditions were kept constant. A graph of milk and water temperature against time was constructed with 95% confidence intervals. The ideal temperature range was considered to be between 56 and 62.5 degrees C. Milk temperature remained between 56 and 62.5 degrees C for between 10 and 15 min depending on the combination of variables. The peak temperature and duration of time in the ideal temperature range was minimally sensitive to volume of milk, starting temperature of milk, and ambient temperature. Pretoria Pasteurisation is feasible and reliable under a range of conditions. The method requires refinement and further testing under different conditions.
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PMID:Pretoria pasteurisation: a potential method for the reduction of postnatal mother to child transmission of the human immunodeficiency virus. 1099 83

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.
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PMID:QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans. 1122 80

Thirty-three HIV-seronegative adults were recruited into a Phase I safety and immunogenicity HIV-1 vaccine trial. The immunogens were as follows: a synthetic, monovalent, octameric HIV-1 MN V3 peptide in aluminum hydroxide (alum) adjuvant administered by intramuscular delivery; and a similar product encapsulated in biodegradable micro-spheres composed of co-polymers of lactic and glycolic acids, administered by the oral route. These were administered in three sequential oral doses, followed by a parenteral boost. No serious adverse experiences were observed. Oral administration of this vaccine, alone or in combination with parenteral boosting, resulted in no significant humoral, cellular, or mucosal immune responses.
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PMID:A Phase I safety and immunogenicity trial of UBI microparticulate monovalent HIV-1 MN oral peptide immunogen with parenteral boost in HIV-1 seronegative human subjects. 1131 97

Some neutralizing epitopes on HIV-1 envelope proteins were shown to induce antibodies that could effectively inhibit the infection of different HIV-1 strains in vitro. But only very low levels of antibodies to these epitopes were determined in the HIV-1 infected individuals. In this study, the aluminum (alum) adjuvant to increase the immunogenicity of the neutralizing epitopes was used. Three epitope-peptides [C-(ELDKWAG)4, C-(RILAVERYLKD-G)2 and C-(GPGRAFY)2], which contain three epitopes (ELDKWA, RILAVERYLKD, GPGRAFY) from the HIV-1 Env proteins, were synthesized and conjugated to carrier protein keyhole limpet hemocyanin (KLH). The epitope-vaccines C-(ELDKWAG)4-KLH and C-(RILAVERYLKD-G)2-KLH in alum induced high levels of epitope-specific antibodies recognizing the epitopes from epitope-peptides C-(ELDKWAG)4 and C-(RILAVERYLKD-G)2, as well as the gp41 C-domain peptides P2 [C-TSLIHSLIEESQNQQEKNEQELLELDKWA (aa 646-674)] and P1 [LQARILAVERYLKDQQL (aa 583-599)] and the recombinant soluble gp41 (rsgp41) bearing both epitopes (antibody titer in rabbit sera was 1:12800-25,600 dilution). Immunoblotting analysis demonstrated that the antibodies in both antisera bound to rsgp41, indicating that both antibodies recognized the natural epitopes on rsgp41 protein. The epitope-vaccines C-(GPGRAFY)2-KLH induced moderate GPGRAFY epitope-specific antibody response with a titer of 1:6,400. In contrast, as it was demonstrated in previous studies, the immunization with rgp160 induced weak antibody response to these three epitopes (titer of 1:400-1600). This suggests that epitope-peptides conjugated to KLH when infected with alum significantly increases immunogenicity of gp41 neutralizing epitopes providing a hope for the development of an HIV-1 vaccine.
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PMID:HIV epitope-peptides in aluminum adjuvant induced high levels of epitope-specific antibodies. 1135 88


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