TB vaccines: progress and problems

Tuberculosis (TB) is the biggest killer worldwide of any infectious disease, a situation worsened by the advent of the HIV epidemic and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. The existing vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has proven inefficient in several recent field trials. There is currently intense research using cutting-edge vaccine technology to combat this ancient disease. However, it is necessary to understand why BCG has failed before we can rationally develop the next generation of vaccines. Several hypotheses that might explain the failure of BCG and the strategies designed to address these shortcomings are discussed.     

Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria

The introduction of Haemophilus influenzae type b conjugate vaccines during the 1990s was followed by dramatic decreases both in the incidence of Haemophilus influenzae type b related invasive disease and in nasopharyngeal carriage of the organism. The extent of this effect has been influenced by the fact that Haemophilus influenzae type b conjugate vaccines reduce nasopharyngeal carriage and induce herd immunity. Based on the success of Haemophilus influenzae type b conjugate vaccines, chemical conjugation has been applied to the development of pneumococcal and meningococcal polysaccharide conjugate vaccines. Evidence has begun to accumulate that these new polysaccharide based conjugate vaccines can also reduce nasopharyngeal carriage and can induce immune responses at the local mucosal level, which may be responsible for these effects. This article reviews recent studies on mucosal immune responses induced by polysaccharide based vaccines and some protein vaccine antigens against several pathogenic nasopharyngeal bacteria, and discusses the mechanisms and functions of these immune responses that may help our understanding of mucosal immune responses to both immunisation and infection.     

Use of attenuated bacteria as delivery vectors for DNA vaccines

Live, attenuated bacterial vaccines (LBV) are promising candidates for the induction of a broad-based immune response directed at recombinant heterologous antigens and the corresponding pathogen. LBVs allow vaccination through the mucosal surfaces and specific targeting of professional antigen-presenting cells located at the inductive sites of the immune system. A novel approach exploits attenuated intracellular bacteria as delivery vectors for eukaryotic antigen-expression plasmids (so-called DNA vaccines). Candidate carrier bacteria include attenuated strains of Gram-positive and Gram-negative bacteria. These bacteria have been shown to deliver DNA vaccines to human cells in vitro and have also proven their in vivo efficacy in several experimental animal models of infectious diseases and different cancers. The clinical assessment of the safety, immunogenicity and efficacy of these candidate strains will be the next challenging step towards live bacterial DNA vaccines.     

New vaccines against enteric bacteria for children in less developed countries

Diarrheal diseases represent a major threat to infant survival in less developed countries. A real opportunity now exists to help alleviate this problem through the development of safe and effective multicomponent whole-bacterial cell vaccine(s) against enterotoxigenic Escherichia coli and Shigella, two important pathogens for which no licensed vaccine exists. What is preventing realization of this achievement is a lack of focus on the unique needs of children in less developed countries, along with committed and sufficient funding directed toward this goal. Live-attenuated and inactivated whole-cell vaccine candidates, some of which have languished too long, are available for testing, which, if performed in a coordinated fashion, can answer key unresolved issues concerning mucosal vaccination against enteric diseases. These candidate vaccines potentially provide a relatively simple intervention which could, if implemented, reduce the impact of these diseases upon the life and productivity of children.     

结核感染T细胞斑点试验在结核诊断与筛查中的价值

目的 探讨结核感染T细胞斑点试验(T-SPOT.TB)在结核诊断与筛查中的价值.方法 对2013年1月至2016年12月在南通市第一人民医院就诊的266个患者分为结核组、非结核组及生物制剂组,抽取静脉血应用结核感染T细胞斑点试验进行检测,同时部分患者进行了结核菌素检测.结果 T-SPOT.TB法诊断TB患者的敏感度为87.9％,阳性预测价值和阴性预测价值分别是43.2％和88.5％,TB组T-SPOT.TB检测阳性率明显高于非TB组(P ＜0.001)和生物制剂组(P＜0.001)的阳性率.而TST试验结果中,TB组阳性率与非TB组、非TB组阳性率与生物制剂组差异均没有统计学意义(P＞0.05),而TB组阳性率与生物制剂组差异有统计学意义(P＜0.05).在所有受试者T-SPOT.TB检测和TST试验的一致性为70.3％(K =0.397),生物制剂组中两者一致性为59.5％ (K=0.313).在TB组和非TB组中,两种方法一致性更高,分别为83.7％(K=0.486)和77.1％ (K=0.437).T-SPOT.TB法中TB组的斑点数显著高于非TB组(P ＜0.001)和生物制剂组(P＜0.001),而非TB组和生物制剂组的斑点数差异没有统计学意义(P＞0.05).结论 T-SPOT.TB检测比结核菌素试验有更高的灵敏度及阴性预测价值,并且不受环境分枝杆菌和BCG接种的影响,使得T-SPOT.TB在结核感染的诊断与筛查中具有较好的临床应用价值.     

TB news

Tuberculosis (TB) requires several different treatment drugs, making daily treatment difficult to maintain. A study of 23 HIV-positive TB patients and 22 HIV-negative TB patients found twice-weekly therapy to be effective. The patients received either daily therapy or therapy three times per week. The therapy consisted of isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for seven months in HIV-positive patients and four months in HIV-negative patients. Compliance was defined as completing eighty percent of the required doses.     

TB or not TB: The role of immunodiagnosis

The evaluation of delayed‐type hypersensitivity immune responses by the tuberculin skin test and, more recently, by ex vivo IFN‐γ release assays (IGRAs) form the basis for the risk assessment for the development of tuberculosis (TB) in close contacts of infective index patients and in immunocompromised hosts. In contrast, immunodiagnosis has little value for the diagnosis of active TB so far. A report in this issue of the European Journal of Immunology [ Eur J Immunol 2012. 42: 2844–2850 ] provides new insight into the phenotypic characteristics and selective recruitment of Ag‐specific T cells to the site of the infection, as analyzed by flow cytometry, which may provide new opportunities for the immune‐based diagnosis of TB in the future.     

Surface plasmon resonance analysis of antipolysaccharide antibody specificity: responses to meningococcal group C conjugate vaccines and bacteria

Antibody (Ab) responses to polysaccharides (PS), such as Neisseria meningitidis group C PS (MCPS), are characterized as being thymus independent and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled with tetanus toxoid or the diphtheria toxin derivative CRM197, elicit thymus-dependent responses. The present study developed a surface plasmon resonance approach to evaluate Ab responses to MCPS conjugate vaccines, including either O-acetylated (OAc+) or de-O-acetylated (OAc-) forms of the PS. The results were generally consistent with those obtained by enzyme-linked immunosorbent assay and showed that sera from mice immunized with conjugate vaccines contain Abs that bind more effectively to OAc+ and OAc- MCPS than sera from mice immunized with fixed bacteria. The data suggest a critical shared or overlapping epitope recognized by all the conjugate vaccine immune sera and strategies for assessing polyclonal Ab avidity.     

The campaign against TB: governments must commit themselves. TB in Africa

This article presents an interview with Pierre Chaulet on the campaign against tuberculosis (TB) in Africa. Chaulet noted during the 9th IUATLD Conference of the Africa Region that the national TB control programs have taken on a new commitment in Africa since the declaration of TB as a global emergency in the 1990s. The TB control program package consists of five principal components: 1) political will of the government and its commitment to support the program; 2) case detection; 3) initiation of short course chemotherapy among detected cases; 4) ensuring the regular supply of essential anti-TB drugs; and 5) establishing a registry and reporting system for program monitoring and evaluation. Of the 40 African countries participating in the conference, 30 have efficient programs. Comparing the management of National TB Control Programs in Francophone and Anglophone Africa, it is noted that both are complementary, although generally, public health issues are more easily integrated into the medical training in the Anglophone countries than they are in the Francophone. Anglophone uses a more comprehensive approach to public health while countries in the Francophone practiced a more traditional university centralization. Finally, Chaulet gives his comment on the role of WHO in addressing concerns over the financial issues involved in TB Control Programs, particularly in the mobilization of resources from nongovernmental organizations and international institutions.     

Anticholera vaccines and vaccination

Cholera is still an important diarrhoeal disease in developing countries. The impact of cholera out-break is tremendous for a country at human and economic level. WHO estimates that diarrhoeal diseases cause about 2.8 million deaths per year in developing countries. Officially, cholera is causing around 120,000 deaths per year. The poorest population (from slums and refugee camps) are the most vulnerable target for cholera infection. Development of simple cheap and effective vaccine is highly recommended. This article aims at giving an update on the currently available and future vaccines for the prevention of diarrhoea due to Vibrio cholerae O1 and O139.