六种阳离子助剂对阿维菌素的增效作用

采用浸虫法和叶片药膜法比较了6种阳离子助剂与阿维菌素混用对小菜蛾Plutella xylostella 3龄幼虫的增效作用,并通过测定助剂对阿维菌素药液物理性状的影响以及助剂对小菜蛾体内超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalases,CAT)和过氧化物酶(peroxidases,POD) 3种保护酶活性的影响等方面对其增效机制进行了初步分析,为阳离子助剂在杀虫剂领域的开发提供一定的依据。结果表明： 在400 mg/L以下,各阳离子助剂单独使用对小菜蛾3龄幼虫均无生物活性,但可明显提高阿维菌素对小菜蛾的药效。两种方法中,浸虫法的增效作用大于叶片药膜法,其中松香酸铜、1427和412103对阿维菌素的增效倍数分别为3.71、2.82和2.72。6种助剂均可明显降低阿维菌素药液的表面张力和接触角及增加药液在甘蓝叶片上的沉积量,但不同助剂间及相同助剂不同浓度间差异虽大多显著; 与增效比结果综合分析表明,助剂的润湿性能与其增效作用之间关系不大。阿维菌素药液分别加入松香酸铜、1427和412103后使试虫体内POD和SOD的活性明显提高,从侧面说明这3种助剂对虫体更具渗透性。     

AS系列佐剂

AS01、AS02、AS03和AS04是由葛兰素史克公司研制的人用疫苗佐剂,属于AS(adjuvant system,AS)系列佐剂。AS01是一种包含单磷酸酰脂质A(3-O-desacyl-4'-monophosphoryl lipid A,MPL)和皂素QS-21的脂质体佐剂,已被用于疟疾疫苗。AS02是含有MPL和QS-21的水包油乳化剂。AS03是包含α-生育酚、角鲨烯、Tween 80的水包油乳化剂,已被用于流感疫苗。AS04是含MPL的铝佐剂,已被用于人乳头瘤病毒疫苗和乙型肝炎病毒疫苗。     

New adjuvants to enhance anticoagulant activity of Warfarin

New adjuvants of warfarin anticoagulant activity have been developed. These compounds, which are 1,4-methano-1,2,3,4-tetrahydroanthracene-9,10-diol derivatives, act synergistically with warfarin to potentiate its anticoagulant effect. None of the compounds tested is an effective oral anticoagulant in the absence of warfarin.     

Increase of non-specific resistance to infection by synthetic adjuvants]

MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status.     

Synthetic glycolipid adjuvants.

In the course of the organic synthesis of model compounds similar in some features to the lipid moiety of endotoxic lipopolysaccharide (LPS), Nacylated-D-glucosamine derivatives were prepared. One of these, N-palmitoyl-D-glucosamine, has been previously found to be mitogenic for athymic nude mouse B cells. This and other N-acylated homologs were tested for adjuvant activity in the immune response to human gamma-globulin (HGG) and sheep red blood cells (SRBC) in mice. Comparable or superior enhancement of the immune response was obtained for these glycolipids when compared to LPS in assays measuring anti-SRBC or HGG hemagglutinin titers. In the determination of hemolytic plaque formation, considerable adjuvant effect was shown by the lauroyl derivative, and less but still significant enhancement was achieved by the N-palmitoyl-D-glucosamine. In the rosette formation assay, in addition to the above two glycolipids, N-oleyl-D-glucosamine showed good adjuvant effect. In the latter two assays, the LPS was a superior adjuvant as compared to the synthetic glycolipids. The radiation protective effect of some of the better synthetic adjuvants was also investigated in mice. It was found that although LPS was more effective in this assay, the N-myristoyl-D-glucosamine and N-decanoyl-D-glucosamine compounds gave a definite protection, since up to 40% of the lethally irradiated (700 R) mice survived.     

Innate immunity and adjuvants

Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection.     

Effect of adjuvants on the humoral immune response to congopain in mice and cattle

ABSTRACT: BACKGROUND: We investigated several adjuvants for their effects on the humoral immune response in both mice and cattle using the central domain of congopain (C2), the major cysteine protease of Trypanosoma congolense, as a model for developing a vaccine against animal trypanosomosis. The magnitude and sustainability of the immune response against C2 and the occurrence of a booster effect of infection, an indirect measure of the presence of memory cells, were determined by ELISA, while spectrofluorometry was used to determine and measure the presence of enzyme- inhibiting antibodies. RESULTS: Mice immunized with recombinant C2 in AdjuphosTM, TiterMaxTM, purified saponin Quil ATM or GERBUTM showed the best response according to the evaluation criteria and these three were chosen for the cattle vaccination study. The animals were challenged with T. congolense four and a half months after the last booster. Cattle immunized with recombinant C2 in purified saponin Quil ATM showed the best antibody response according to the measured parameters. CONCLUSIONS: We identified purified saponin Quil ATM as a good adjuvant for immunizations with C2. The results from this study will be useful in future attempts to develop an effective anti-disease vaccine against African trypanosomosis.     

新型疫苗佐剂的研究进展

近年来,核酸疫苗、基因工程疫苗、合成肽疫苗等新型疫苗的研究取得快速的发展,但这些疫苗与传统的灭活或活体疫苗相比,往往存在免疫原性差等问题,因此需要佐剂来增强其作用.佐剂已被证明是疫苗中的关键成分,佐剂种类众多,尚无统一的分类方法,目前应用最多的佐剂是铝佐剂和弗氏佐剂,但随着新型疫苗的开发,新型佐剂的开发必不可少.根据目...     

Cytokines as potential vaccine adjuvants

There is a compelling clinical need for adjuvants suitable for human use to enhance the efficacy of vaccines in the prevention of life-threatening infection. Candidate populations for such vaccine-adjuvant strategies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. In addition, adjuvants that would increase the efficiency of vaccination with such vaccines as those directed against hepatitis B andStreptococcus pneumoniae would have an even greater general use. Cytokines, as natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work utilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma-interferon, tumor necrosis factor, and granulocyte-monocyte-colony stimulating factor has shown that cytokines do have vaccine adjuvant activity. However, in order to optimize adjuvant effect and minimize systemic toxicity, strategies in which the cytokine is fused to the antigen, or the cytokine is presented within liposomes or microspheres appear to be necessary to make this a practical approach suitable for human use. There is much promise in this approach, but there is much work to be accomplished in order to optimize the pharmacokinetics of cytokine administration as well as its side effect profile.Abbreviations IL interleukin - TNF tumor necrosis factor - NK natural killer - pIL-1 interleukin-1 peptide - LPS lipopolysaccharide - r recombinant - HSV-2 herpes simplex virus 2 - gamma     

Biologic adjuvants for fracture healing

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Advances in vaccine adjuvants.

Currently, aluminum salts and MF59 are the only vaccine adjuvants approved for human use. With the development of new-generation vaccines (including recombinant subunit and mucosal vaccines) that are less immunogenic, the search for more potent vaccine adjuvants has intensified. Of the novel compounds recently evaluated in human trials, immunostimulatory molecules such as the lipopolysaccharide derived MPL and the saponin derivative QS21 appear most promising, although doubts have been raised as to their safety in humans. Preclinical work with particulate adjuvants, such as the MF59 microemulsion and lipid-particle immune-stimulating complexes (Iscoms), suggest that these molecules are also potent elicitors of humoral and cellular immune responses. In addition, preclinical data on CpG oligonucleotides appear to be encouraging, particularly with respect to their ability to selectively manipulate immune responses. While all these adjuvants show promise, further work is needed to better define the mechanisms of adjuvant action. Ultimately, the development of more potent adjuvants may allow vaccines to be used as therapeutic, rather than prophylactic, agents.