Acquired immunity and epidemiology of Schistosoma haematobium

Human immune responses to schistosome infection have been characterized in detail. But there has been controversy over the relative importance of ecological factors (variation in exposure to infection) and immunological factors (acquired immunity) in determining the relationships between levels of infection and age typically found in areas where infection is endemic. Independent effects of exposure and age on the rates of reinfection with Schistosoma haematobium after chemotherapy have been demonstrated in the Gambia and Zimbabwe. This age effect could be the result of acquired immunity to infection. Indeed, allowing for variation in exposure and age, low rates of reinfection in the Gambia are correlated with high amounts of specific IgE antibodies--human IgE can kill S. mansoni schistosomulae in vitro. Further, animals can acquire immunologically mediated resistance to S. mansoni infection, although nonimmunological factors could also be involved. Acquisition of this immunity seems to be related to the cumulative effects of repeated infection and provides only partial protection. These characteristics are consistent with immuno-epidemiological data for both S. mansoni and S. haematobium infections of humans. We have now analysed age-prevalence data for human infection with S. haematobium, and find patterns of variation that are indeed consistent with the epidemiological effects of acquired immunity predicted by mathematical models.     

Transmission potential of smallpox in contemporary populations.

Despite eradication, smallpox still presents a risk to public health whilst laboratory stocks of virus remain. One factor crucial to any assessment of this risk is R0, the average number of secondary cases infected by each primary case. However, recently applied estimates have varied too widely (R0 from 1.5 to >20) to be of practical use, and often appear to disregard contingent factors such as socio-economic conditions and herd immunity. Here we use epidemic modelling to show a more consistent derivation of R0. In isolated pre-twentieth century populations with negligible herd immunity, the numbers of cases initially rose exponentially, with an R0 between 3.5 and 6. Before outbreak controls were applied, smallpox also demonstrated similar levels of transmission in 30 sporadic outbreaks in twentieth century Europe, taking into account pre-existing vaccination levels (about 50%) and the role of hospitals in doubling early transmission. Should smallpox recur, such estimates of transmission potential (R0 from 3.5 to 6) predict a reasonably rapid epidemic rise before the implementation of public health interventions, because little residual herd immunity exists now that vaccination has ceased.     

Cell-mediated immunity in the liver of mice vaccinated against malaria.

Mice can be protected against several species of lethal malaria infection by vaccination, and their recovery correlates well with increased anti-malarial antibody levels, particularly IgG (ref.2). However, there is also a good correlation between protection by vaccines and priming for delayed-type hypersensitivity in the skin, although there is no obvious explanation for this effect. We now report an apparent relationship between protection and a cell-mediated immune response involving the migration of various types of cell capable of killing malaria parasites in vitro to the liver. We suggest that the effect of vaccination is to bring together parasites, specific antibody and nonspecific cytotoxic cells, and that the liver may be a major site for their interaction.     

Immunity to intestinal parasites

Intestinal parasites are common in man and animals and can cause severe disease. Knowledge of immunity to such infections is limited and comes largely from studies using laboratory host-parasite systems. Understanding how immunity can operate, and why it often does not, is not only of intrinsic interest but necessary for the development of immunological methods of control.     

Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium

A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.     

Prophylactic cancer vaccine,from concept to reality？

The demonstration that for infectious diseasesvaccine-induced immunity is in principle only effectivebefore rather than after infection occurs, provides valuableinsights in understanding the nature of immune system andthe challenges in cancer treatment. Besides the alreadyknown underlying counter-back mechanisms, the astro-nomical numbers of tumor cells in established tumorscould overwhelm the limited amount of specific T cellsinduced by vaccination, which may account for the modestefficiency of immunotherapy against cancer. We speculatethat the long window period for cancer development willallow immune-intervening strategies （e.g., the proper pro-phylactic vaccination） to promote adaptive mechanismstoward an enhanced immunosurveillance, which couldeffectively eradicate or at least control the few precancer-ous cells undergoing neoplastic transformation during earlypremalignant stages in cancer development, and protect thehost from lethal tumor formation. It should be emphasizedthat the pre-cancer-associated antigens but not the tumor-associated antigens seem to be the suitable antigens fordesigning prophylactic cancer vaccines. In addition, anideal prophylactic cancer vaccine may contain multiplepre-cancer-associated antigens, which will provide broadand effective immune protection in a heterogeneous humanpopulation. Finally, we demonstrated that placenta-derivedgp96, which can be readily obtained in high amount forvaccination, has the ability to initiate antitumor T-cellimmunity via association with multiple embryo-cancerantigens. Further understanding placental gp96 associatedwith carcinoembryonic antigen repertoires that orchestrateimmune defense networks against cancer formation willallow to provide an effective prophylactic approach incancer prevention.     

基于 SIR 传染病模型的印度新冠疫情波及影响分析

针对印度新型冠状病毒肺炎(COVID-19)疫情的传播,建立通过设定目标函数求最优解来确定模型未知参数的 SIR 传染病动力学模型。 首先通过线性回归拟合参数范围,设定目标函数作为约束条件,结合龙格-库塔法,借助 Matlab 软件确定参数值最优解,进行 SIR 模型拟合和预测,发现印度疫情拐点将出现在 2021 年 5 月 8 日左右,结合预测数据推导未来每日新增及累计新增病例数,虽未来 100 d 内将持续出现新增病例,但疫情现期已经有消退趋势;其次考虑印度变种病毒 B. 1. 617 以及当下疫苗接种情况的影响,建立加入疫苗影响因素的 SIR 预测模型,通过进行疫苗接种灵敏度分析模拟出印度疫苗接种率大约需要达到 75%,考虑有效保护率则接种率需要高达 95%,才可以建立起群体免疫屏障;最后通过基本传染数验证了疫苗接种率,并对新冠波及影响做出了相应对策分析。     

Vaccination with purified microgamete antigens prevents transmission of rodent malaria

Malaria vaccination with preparations of microgametes has been shown to inhibit transmission of Plasmodium spp. to the mosquito vectors of avian, rodent and simian parasites. This transmission-blocking immunity results from the induction of microgamete-agglutinating antibodies in the vaccinated host which, when ingested in a mosquito blood meal, react with exflagellating microgametes in the midgut to prevent fertilization and oocyst development. Here we have passively transferred the immunity with gamete-specific monoclonal antibodies raised against the rodent malaria parasite Plasmodium yoelii nigeriensis, and an IgG2a isotype monoclonal antibody from a hybridoma cell line, PYG-1, has been used to identify the target antigens on the gametes and to affinity-purify sufficient quantities of specific gamete antigen to facilitate vaccination studies. This transmission-blocking monoclonal antibody immunoprecipitated microgamete antigens of apparent relative molecular mass (Mr), 67K (67,000), 59K, 57K, 42K and 35K. Immunization of mice with these proteins before infection and mosquito feeding led to a 85-99.7% reduction in transmission to the mosquito vector; vaccination via intravenous or intramuscular routes was equally effective and did not require an adjuvant.     

Helper T cells regulate type-2 innate immunity in vivo

Type-2 immunity requires orchestration of innate and adaptive immune responses to protect mucosal sites from pathogens. Dysregulated type-2 responses result in allergy or asthma. T helper 2 (T(H)2) cells elaborate cytokines, such as interleukin (IL)-4, IL-5, IL-9 and IL-13, which work with toxic mediators of innate immune cells to establish environments that are inhospitable to helminth or arthropod invaders. The importance of T(H)2 cells in coordinating innate immune cells at sites of inflammation is not known. Here we show that polarized type-2 immune responses are initiated independently of adaptive immunity. In the absence of B and T cells, IL-4-expressing eosinophils were recruited to tissues of mice infected with the helminth Nippostrongylus brasiliensis, but eosinophils failed to degranulate. Reconstitution with CD4 T cells promoted accumulation of degranulated IL-4-expressing cells, but only if T cells were stimulated with cognate antigen. Degranulation correlated with tissue destruction, which was attenuated if eosinophils were depleted. Helper T cells confer antigen specificity on eosinophil cytotoxicity, but not cytokine responses, so defining a novel mechanism that focuses tissue injury at sites of immune challenge.     

Population dynamics of Schistosoma mansoni in mice repeatedly exposed to infection

Studies of host resistance to parasite infection are usually based on experimental designs involving a primary infection and subsequent challenge exposure, resistance being recorded as the percentage reduction in parasite establishment in challenged hosts when compared with that in uninfected animals. Few studies have focused on the dynamic nature of helminth establishment and mortality (and their presumed dependency on the rate of current exposure and past experiences of infection) in hosts repeatedly exposed to low levels of infection. Here, we report the results of population studies on the dynamics of resistance to Schistosoma mansoni infection (a helminth parasite) in mice repeatedly exposed to cercarial invasion. Parasite burdens created by different levels and durations of exposure to infection reflect a dynamic interplay between rates of helminth establishment and mortality. Depending on the intensity of exposure, changes in worm load with duration of host infection vary from monotonic growth to a stable average parasite burden to convex curves in which the average load attains a maximum value before decaying in old animals. These trends are similar to observed patterns of S. mansoni infection in human communities.     

Innate defence: evidence for memory in invertebrate immunity

Acquired immunity in vertebrates is characterized by immunological memory and specificity, whereas the innate defence systems of invertebrates are assumed to have no specific memory. Here we use a model system of a copepod, which is a minute crustacean, and a parasitic tapeworm to show that the success of reinfection depends on the antigenic resemblance between the consecutively encountered parasites. This finding indicates that an invertebrate defence system may be capable of specific memory.     

Vaccination against ovine cysticercosis using a defined recombinant antigen

Cysticercosis caused by larval tapeworms is a major public health problem and a cause of substantial economic losses in the farm-animal industries. Taenia ovis in sheep is a particularly important example. Immunity to reinfection with the larvae has a central role in regulating natural transmission of the parasites, and vaccination with antigens from the early larval oncosphere stage can induce complete protection against infection. As it is impractical to obtain enough oncospheres for a commercial vaccine against these tapeworms, an alternative approach is to use recombinant DNA methods to generate a cheap and plentiful supply of antigens. We report here the expression in Escherichia coli of complementary DNA encoding T. ovis antigens as fusion proteins with the Schistosoma japonicum glutathione S-transferase. Vaccination of sheep with these fusion proteins gave significant, although not complete, immunity against challenge infection with T. ovis eggs. Commercial development of a vaccine is being pursued.     

Co-option of a default secretory pathway for plant immune responses

Cell-autonomous immunity is widespread in plant-fungus interactions and terminates fungal pathogenesis either at the cell surface or after pathogen entry. Although post-invasive resistance responses typically coincide with a self-contained cell death of plant cells undergoing attack by parasites, these cells survive pre-invasive defence. Mutational analysis in Arabidopsis identified PEN1 syntaxin as one component of two pre-invasive resistance pathways against ascomycete powdery mildew fungi. Here we show that plasma-membrane-resident PEN1 promiscuously forms SDS-resistant soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complexes together with the SNAP33 adaptor and a subset of vesicle-associated membrane proteins (VAMPs). PEN1-dependent disease resistance acts in vivo mainly through two functionally redundant VAMP72 subfamily members, VAMP721 and VAMP722. Unexpectedly, the same two VAMP proteins also operate redundantly in a default secretory pathway, suggesting dual functions in separate biological processes owing to evolutionary co-option of the default pathway for plant immunity. The disease resistance function of the secretory PEN1-SNAP33-VAMP721/722 complex and the pathogen-induced subcellular dynamics of its components are mechanistically reminiscent of immunological synapse formation in vertebrates, enabling execution of immune responses through focal secretion.     

Specific and nonspecific immunisation against parasitic infections

Parasitic diseases present major problems to man and his domesticated animals but do not respond easily to conventional vaccination procedures. Vaccines including attenuated stains, killed parasites, homogenates and soluble extracts all produce varying degrees of protection but controlled infections and immunisation with heterologous species or nonspecific antigens also induce protective immunity.     

慢性乙型肝炎临床治疗的现状与挑战

 病毒本身和机体免疫应答是影响HBV感染病情进展和临床转归的重要因素。目前免疫学研究及临床观察结果表明,单纯的抗病毒治疗无法重建慢性乙型肝炎患者的抗病毒免疫功能,因而无法彻底治愈HBV感染。联合新的免疫治疗策略,根据疾病的不同阶段采取针对性的治疗方案,可能是实现HBV感染治愈的有效方法。本文综述慢性乙型肝炎治疗的现状与进展。     

Optimal reactive vaccination strategies for a foot-and-mouth outbreak in the UK

Foot-and-mouth disease (FMD) in the UK provides an ideal opportunity to explore optimal control measures for an infectious disease. The presence of fine-scale spatio-temporal data for the 2001 epidemic has allowed the development of epidemiological models that are more accurate than those generally created for other epidemics and provide the opportunity to explore a variety of alternative control measures. Vaccination was not used during the 2001 epidemic; however, the recent DEFRA (Department for Environment Food and Rural Affairs) contingency plan details how reactive vaccination would be considered in future. Here, using the data from the 2001 epidemic, we consider the optimal deployment of limited vaccination capacity in a complex heterogeneous environment. We use a model of FMD spread to investigate the optimal deployment of reactive ring vaccination of cattle constrained by logistical resources. The predicted optimal ring size is highly dependent upon logistical constraints but is more robust to epidemiological parameters. Other ways of targeting reactive vaccination can significantly reduce the epidemic size; in particular, ignoring the order in which infections are reported and vaccinating those farms closest to any previously reported case can substantially reduce the epidemic. This strategy has the advantage that it rapidly targets new foci of infection and that determining an optimal ring size is unnecessary.     

寄生虫与宿主的相互作用

通过对寄生虫与宿主的相互关系及影响因素进行研究,以有效地控制寄生虫病的发生.结果:不同种类的寄生虫具有不同的亲和性,可在机体的不同脏器或组织寄生.当有两种或两种以上的寄生虫感染时,它们通过相互协同或相互拮抗,共同参与寄生虫抗宿主反应,引起机械性损伤、营养不良、变态反应等.同时,机体对入侵的寄生虫产生一系列免疫反应,及时清除入侵的寄生虫,并具有抵抗再感染的能力,或形成免疫耐受.     

Vaccination and herd immunity to infectious diseases

An understanding of the relationship between the transmission dynamics of infectious agents and herd immunity provides a template for the design of effective control programmes based on mass immunization. Mathematical models of the spread and persistence of infection provide important insights into the problem of how best to protect the community against disease.     

Modelling vaccination strategies against foot-and-mouth disease

Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, 'predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.