A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

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钩虫病感染者免疫球蛋白水平、临床特点及胃肠镜下形态分析

目的分析钩虫病感染者血清免疫球蛋白(Ig)A、IgG、IgM和IgE水平,临床特点及胃肠镜下形态。方法分析16例钩虫病感染者的临床资料,观察患者的临床表现、Ig水平、血常规检查结果、胃肠镜检查结果及治疗结果。结果 16例患者的IgE水平明显高于正常参考上限值;IgA、IgG、IgM水平与正常参考上限值比较,差异不明显。经诊断患者的钩虫分布情况:十二指肠降部8例(50.00%),十二指肠球部5例(31.25%),回肠末端3例(18.75%),升结肠1例(6.25%),其中十二指肠及回肠末端均见钩虫者1例(6.25%)。所有患者均予阿苯达唑片驱虫治疗,治疗后1个月复查见贫血得到纠正,消化道症状得以缓解,复查胃肠镜未见虫体,均治愈。结论钩虫病感染者的IgE水平明显升高,胃肠镜检查是确诊钩虫病的重要手段,尤其是要加强对十二指肠降部的检查,并在确诊后及时给予正规治疗措施。     

High-dose intravenous immunoglobulin therapy improved muscle strength in a patient with multifocal motor neuropathy and antibodies against the glycolipid LK1

We report improvement in muscle strength in a patient with multifocal motor neuropathy (MMN) when given high-dose intravenous immunoglobin (i.v.-Ig) treatment. The patient had asymmetrical limb weakness, atrophy and absent or weak reflexes, but no sensory disturbances. Neurography showed multiple conduction blocks in peripheral motor nerves but no sensory nerve abnormalities. Serum and anti-GM1 antibodies were not found, however, the patient had serum antibodies against the glycolipid LK1, an epitope found both in glycolipid and also in some glycoproteins in peripheral nerve myelin. Muscle strength improved 5 days after i.v.-Ig therapy, and lasted about 10 weeks. Repeated courses of treatment resulted in similar improvement. This is, to our knowledge, the first patient reported with MMN found to have antibodies against the glycolipid LK1.     

Substantial inhibition of neo-intimal response to balloon injury in the rat carotid artery using a combination of antibodies to platelet-derived growth factor-BB and basic fibroblast growth factor

Thirty percent of patients undergoing percutaneous transluminal coronary angioplasty develop recurrent disease within a year. This is usually due to the rapid accumulation of intimal smooth muscle cells and extracellular matrix, which causes luminal narrowing, and is probably orchestrated by several mitogenic and chemotactic factors, of which platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) appear to be particularly important. We have investigated the effects of administering a combination of neutralizing antibodies directed against PDGF-BB and bFGF on neo-intima development following balloon catheter injury in the rat carotid artery. Purified sheep anti-PDGF-BB and anti-bFGF immunoglobulins (IgGs) were administered singly and in combination prior to mechanical injury and daily until sacrifice, 8 days later. Plasma titres of exogenous anti-PDGF-BB and anti-bFGF were maintained at levels 10–20-fold higher than those required to neutralise the mitogenic and chemotactic effects of 20 ng/ml of PDGF-BB, or 10 ng/ml bFGF in vitro. Used singly, anti-PDGF IgG treatment was associated with a 47% reduction in intimal thickness and a 59% reduction in intimal:medial area ratio; anti-bFGF IgG administration caused a 53% reduction in intimal thickness, and a 50% reduction in intimal:medial area ratio. Treatment with a combination of these antibodies resulted in a 83.8% reduction in intimal thickness (P<0.05), and a 91% reduction in intimal:medial area ratio (P<0.01). The latter treatment was also associated with a significantly higher intimal cell density (14.2±1.6×10³ nuclei/mm²) compared to animals receiving non-immune IgG (7.8±0.8×10³ nuclei/mm²; P<0.025), although intimal and medial cell proliferation indices were not significantly different between the groups (P>0.05). Our results suggest that in this particular model, PDGF-BB and bFGF are the major factors controlling neointimal hyperplasia, and that these growth factors are operating principally via an effect on smooth muscle cell migration and extracellular matrix protein accumulation.     

Dietary Vitamin E Modulation of Cytokine Production by Splenocytes and Thymocytes from Alcohol-Fed Mice

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably afffecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and inter-feron-γ by concanavalin A (Con A)-stimulated splenocytes and in terleukin-6 and tumor necrosis factor-a by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccha-ride-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleu-kin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin- 4 and interferon-γ production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supple-mentation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.     

Immunoglobulin Y Levels in Egg Yolk From Three Chicken Genotypes

Laying hens are very efficient producers of antibodies and provide an interesting alternative for large-scale production of specific antibodies. These antibodies also have biochemical advantages over mammalian antibodies (e.g. rabbit antibodies) that can be used to improve immunoassays where antibodies are used. The concentration of IgY in egg yolk is an important production parameter. The purpose of this study was to investigate the genetic variation of IgY levels in egg yolk. We have compared IgY concentrations in egg yolks from two lines, selected for egg production traits at the Swedish University for Agricultural Sciences (Single Comb White Leghorn and Rhode Island Red) and a cross between the two lines (SLU-1392). Single Comb White Leghorns have the highest mean concentration of yolk IgY, 2.21 mg ml^-1 compared to SLU-1392 1.95 mg ml^-1 and Rhode Island Red 1.68 mg ml^-1. The cross thus had an intermediate IgY concentration in relation two the two other lines. There were great differences between individual animals within each line. Our results indicate that it should be possible to increase yolk antibody production by using a high producing chicken line and by genetic selection within the line. We found three individuals with very low yolk IgY concentrations among the Rhode Island Red hens. Newly hatched chickens with limited amounts of IgY from the hen may be more susceptible to infections.     

Evidence for a human IgG1 class switch program

In activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1-expressing human B cells, immortalized by Epstein-Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1-expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.