Veterinary epidemiology: vaccination strategies for foot-and-mouth disease

When foot-and-mouth disease struck the United Kingdom in 2001, the traditional 'stamping out' policy of 1967-68 was supplemented by the pre-emptive culling of animals in premises contiguous to infected premises. A model proposed by Tildesley et al. indicates that the introduction of vaccination should at least halve the number of premises that would need to be subjected to culling in the event of another outbreak. We contest, however, that the overlapping confidence intervals of the outputs of their model, and the inconsistency of their results compared with those from previous models, call into question the model's value as a decision tool, while adding little to the recognized tenet of ring vaccination.     

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.     

抗FMDV基因疫苗的研究进展

口蹄疫是由口蹄疫病毒引起的猪、牛、羊等偶蹄动物一种高接触性传染病.口蹄疫一旦爆发和流行,会使家畜生产性能降低,给养殖户造成重大损失,给公共卫生造成重大的影响.随着弱毒苗禁用和灭活苗的减少使用,新型疫苗的研究成为热点.自1990年首次出现基因疫苗的研究报道之后,基因疫苗已经成为疫苗研究领域中的一大热点,因此该文对近年来国内外口蹄疫基因疫苗研究的主要进展进行综述.     

A型口蹄疫病毒VP1免疫活性肽基因串联片段的化学合成及克隆与表达

A型口蹄疫病毒（FMDV）VP1蛋白的141～160和200～213位氨基酸序列是决定FMDV免疫原性的抗原决定簇片断．人工合成一个免疫活性肽基因的串连片段（20AA－14AA-20AA）、全部选用大肠杆菌偏爱密码子．在5’端带有EcoR1位点和一个起始密码子ATG，在3’端带有BamH1位点和一个终止密码子TGA．利用这两个酶切位点把该基因连接到pWR590质粒上．并筛选高表达的菌株．结果表明该融合蛋白在大肠杆菌JM101中能高表达．经斑点ELISA实验证明．大肠杆菌细胞中表达的融合蛋白有A型FMDV抗原活性．     

CpG DNA enhances the immune responses elicited by the DNA vaccine against foot-and-mouth disease virus in guinea pigs

CpG DNA is DNA sequence that has immune stimulatory effects. Several lines of investigation over the past few years indicate that CpG DNA plays an important role in the induction of immune responses to DNA vaccines. In this study, CpG DNA-containing synthetic oligodeoxynucleotide (CpG-ODN) was cloned into the eukaryotic expression plasmid encoding a fusion protein containing b- galactosidase from E. coli and immunogenic epitopes of foot- and-mouth disease virus (FMDV) type O, and the immune responses induced by the plasmid were assayed. The results showed that guinea pigs immunized with the recombinant plasmid containing CpG-ODN generated a higher level of FMDV-neutralizing antibody and a stronger T cell proliferative response and protection against viral challenge than those receiving the plasmid containing no CpG-ODN. Our study demonstrated that it is an effective route to enhance the efficacy of DNA vaccines by inserting exogenous CpG DNA into the plasmids, and the DNA vaccine developed here is a promising candidate to prevent FMDV infection.     

两类不同免疫策略下的SIR流行病模型

研究了两类不同免疫方式下具有饱和传染力的SIR流行病模型的动力学行为.在连续免疫接种方式下,确定了基本再生数R0.用Lassalle定理和Poincare-Bendixon的三分法定理得到疾病消除平衡点和地方病平衡点全局渐近稳定的条件.在脉冲免疫接种方式下,确定了基本再生数R.利用脉冲微分方程的Floquet乘子理论和比较定理,研究了疾病消除周期解的全局渐近稳定性和系统的一致持久性.结果表明,当基本再生数小于1时,该传染病将逐渐消失;当基本再生数大于1时,该传染病将流行,成为地方病.     

口蹄疫病毒持续感染的研究进展

口蹄疫病毒(foot-and-mouth disease virus,FMDV)能引起偶蹄动物患一种名为口蹄疫(foot-and-mouth disease,FMD)的高度接触性、发热性、急性的传染病.FMD的大规模爆发会导致整个国家或地区的动物和动物相关制品产量降低、贸易受限,造成巨大的经济损失.FMDV持续感染是造成FMDV容易蔓延并难以根除的重要原因.该文综述了FMDV持续感染期间病毒在体内的存在位置与感染特性,并以病毒与宿主细胞、宿主免疫系统之间的相互作用为重点,介绍了持续感染相关机制研究进展,总结了疫情防控相关策略,以期为解决FMDV持续感染问题提供参考.     

Chemical basis of antigenic variation in foot-and-mouth disease virus

One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.     

Low-coverage vaccination strategies for the conservation of endangered species

The conventional objective of vaccination programmes is to eliminate infection by reducing the reproduction number of an infectious agent to less than one, which generally requires vaccination of the majority of individuals. In populations of endangered wildlife, the intervention required to deliver such coverage can be undesirable and impractical; however, endangered populations are increasingly threatened by outbreaks of infectious disease for which effective vaccines exist. As an alternative, wildlife epidemiologists could adopt a vaccination strategy that protects a population from the consequences of only the largest outbreaks of disease. Here we provide a successful example of this strategy in the Ethiopian wolf, the world's rarest canid, which persists in small subpopulations threatened by repeated outbreaks of rabies introduced by domestic dogs. On the basis of data from past outbreaks, we propose an approach that controls the spread of disease through habitat corridors between subpopulations and that requires only low vaccination coverage. This approach reduces the extent of rabies outbreaks and should significantly enhance the long-term persistence of the population. Our study shows that vaccination used to enhance metapopulation persistence through elimination of the largest outbreaks of disease requires lower coverage than the conventional objective of reducing the reproduction number of an infectious agent to less than one.     

Evolution and molecular epidemiology of foot-and-mouth disease virus in China

Foot-and-mouth disease (FMD),caused by foot-and-mouth disease virus (FMDV),is considered one of the most important viral diseases of cloven-hoofed animals,causing severe economic losses in affected regions of the world.Three serotypes (A,O,and Asia 1) of FMDV have been identified in China since 1958.In addition,the occurrence of novel subtypes within these serotypes has made the epidemiology of FMDV more complicated over the last few years.In this review,we summarize the history and the current epidemiological situation in China,genetic diversity (e.g.,quasispecies dynamics,antigenic heterogeneity,and functional constraints),intertypic recombination,and the evidence for positive selection of different FMDV serotypes.We also assess these genetic data to understand the origin,evolution,and transmission of FMDV,the findings of which may be useful in developing control measures for future epidemics.     

The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution

The structure of foot-and-mouth disease virus has been determined at close to atomic resolution by X-ray diffraction without experimental phase information. The virus shows similarities with other picornaviruses but also several unique features. The canyon or pit found in other picornaviruses is absent; this has important implications for cell attachment. The most immunogenic portion of the capsid, which acts as a potent peptide vaccine, forms a disordered protrusion on the virus surface.     

Modelling disease outbreaks in realistic urban social networks

Most mathematical models for the spread of disease use differential equations based on uniform mixing assumptions or ad hoc models for the contact process. Here we explore the use of dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations. The graphs are generated by large-scale individual-based urban traffic simulations built on actual census, land-use and population-mobility data. We find that the contact network among people is a strongly connected small-world-like graph with a well-defined scale for the degree distribution. However, the locations graph is scale-free, which allows highly efficient outbreak detection by placing sensors in the hubs of the locations network. Within this large-scale simulation framework, we then analyse the relative merits of several proposed mitigation strategies for smallpox spread. Our results suggest that outbreaks can be contained by a strategy of targeted vaccination combined with early detection without resorting to mass vaccination of a population.     

大学生应对就业困难的策略探讨

当前大学毕业生的就业问题日渐突出。从大学生群体来说,当务之急是要调整心态、积极面对。要充分了解自己,确立职业目标;积极交往,锻炼沟通技巧;整合资源,努力争取生涯发展机会。     

Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants

Study of the immune response to synthetic antigens has shown that uncoupled peptides can realize their potential as vaccines only if they contain domains that react with helper T-cell receptors and Ia antigens in addition to antibody binding sites. Here we consider whether genetically restricted non-responsiveness to an uncoupled peptide could be overcome by synthesizing a peptide with an additional helper T-cell epitope from a different protein. We demonstrate that H-2d mice, which are non-responders to the 141-160 VP1 peptide of foot-and-mouth disease virus (FMDV), can be converted into responders by immunization with peptides containing the FMDV sequence with defined 'foreign' helper T-cell determinants from ovalbumin or sperm whale myoglobin. Furthermore, the virus-neutralizing activity of the antibody raised against peptide was dependent on the determinant used. Thus, FMDV peptides with the added sequences 323-339 from ovalbumin and 132-148 from sperm-whale myoglobin elicited a high degree of neutralizing activity in B10.D2 mice. The sera from mice which received the peptide with the added sequence 105-121 from sperm whale myoglobin did not neutralize the virus, although they had high levels of anti-141-160 FMDV peptide activity. Our data indicate that the T-cell help given by the 'foreign' epitopes is B-cell clone specific. These results are likely to have important implications for the design of peptide vaccines.