Challenge exposure of sheep immunized with live vaccine and culture supernatant of Mannheimia haemolytica A1: Effects of revaccination

Vaccination against Mannheimia haemolytica is a routine procedure in sheep farming, being repeatedly performed on the recommendations of commercial veterinary manufacturers or due to outbreaks of respiratory disease. However, the consequences of repeat vaccination after a short period, using live vaccines or culture supernatant (CS), have not been established, and its benefits are unknown. This study aims to evaluate, in a challenge exposure, the effects of revaccinating sheep with this type of biological product. Thus, 20 mixed-breed, 6–9-month-old sheep were divided into four groups, with five animals in each. Animals in group I were inoculated subcutaneously with 2 ml of a 1 × 10⁹ CFU/ml suspension of bacteria in the exponential growth phase. Group II was inoculated with the same bacterial concentration but in the stationary phase. Animals in group III were inoculated with 3 ml of CS and group IV with saline solution, as control. Each group was immunized again 14 days later, following the same guidelines. On day 21, they were intranasally exposed to parainfluenza-3 virus (PI-3). On day 27, they were challenged with a transthoracic injection of live M. haemolytica (2 × 10⁹ CFU/ml). In this experiment, the levels of agglutinating and antileukotoxin antibodies were evaluated through indirect hemagglutination and toxin neutralization assays. During the first 24 h post-challenge, four animals in group I died, three in group II and two in group III, even though they had developed significant levels of agglutinating and antileukotoxin antibodies. Only one animal from the control group died. Thus, contrary to the development of improved protection due to continuous immunizations with live bacteria or CS, a negative effect was observed. This can be explained as the result of a hypersensitivity type III reaction, due to the significant decrease in agglutinating antibodies observed shortly after the challenge, indicating the formation of immune complex, which triggered the release of chemical mediators of inflammation that, finally, promoted edema and pulmonary congestion.     

Increased extracellular pressure provides a novel adjuvant stimulus for enhancement of conventional dendritic cell maturation strategies

Dendritic cell (DC)-based vaccine strategies have gained increasing popularity in recent years. Methods for ex vivo generation of immunocompetent mature DCs still require optimization. DCs have been shown to phenotypically mature under elevated pressure. We compared the effects of pressure on DC maturation with LPS- and cytokine-stimulation. Human monocyte-derived immature or LPS- and cytokine-matured DCs were exposed to ambient or 40 mmHg increased pressure for 12 h, then assessed for expression of CD80, CD86, CD40, MHC-I/II, and inflammatory cytokine production. DCs were also evaluated for capacity to stimulate T-cell proliferation by co-culture with allogeneic lymphocytes. Pressure significantly increased cytokine production and expression of all surface molecules on immature DC other than MHC-I and CD40. Pressure/LPS-treated DCs displayed further upregulation of MHC-I, CD40, and IL-12p70. Cytokine-matured DCs appeared less responsive to pressure. T-cell proliferation correlated with MHC expression. Results suggest mechanical stimulation of DCs may provide a useful adjuvant to TLR-agonist maturation strategies.     

Vaccines against protozoal diseases of veterinary importance

Abstract Protozoan parasites are important animal and human pathogens. At present, most of these infections are controlled by chemotherapy. In addition, vaccines are available for some of these diseases. There is, however, still an urgent need for the development of vaccines against protozoal diseases, since the current array of available vaccines is very limited. This review describes the different approaches that have been taken to develop such vaccines and discusses the difficulties that hampered vaccine development. Many of the problems are related to the complex life cycle of these parasites and the virtual lack of mass in vitro culture systems. We also give an overview of the commercial and non-commercial vaccines that do exist at present. Finally, we describe the future directions of this interesting field. New techniques and strategies include parasite cultivation methods and recombinant-DNA techniques, such as vector vaccines and DNA-vaccines. Moreover, these approaches are complemented by the development of sophisticated adjuvants; the coupling of immunoprotective molecules to entities with adjuvant activity or the use of cytokines, e.g. IL-12. Through these innovations new vaccines against protozoal diseases will become available in the near future.     

Feline immunodeficiency virus vaccine: Implications for diagnostic testing and disease management

Feline immunodeficiency virus (FIV) is a common feline pathogen, with an overall infection prevalence of approximately 11% in cats worldwide. Most infected cats eventually succumb due to direct viral effects or, more commonly, to secondary infections resulting from virus-induced immunosuppression. FIV infection is considered lifelong, and diagnosis most often relies on detection of virus-specific antibodies. A currently available whole virus, adjuvanted, inactivated FIV vaccine induces antibodies in vaccinates that is indistinguishable from those induced by infection. As a result, currently available diagnostic tests cannot reliably distinguish vaccinated cats from infected cats, or from cats that are both vaccinated and infected. From both an epidemiologic and an individual cat perspective, it is impossible to determine whether use of this vaccination is more beneficial than it is harmful.     

Prevalence of Met-203 type spaA variant in Erysipelothrix rhusiopathiae isolates and the efficacy of swine erysipelas vaccines in Japan

Since 2009, erysipelas infection among pigs in Japan has been increasing. This study investigated the prevalence, and characteristics of Erysipelothrix rhusiopathiae isolates in Japan from 2008 to 2010 and assessed the efficacy of current commercial erysipelas vaccines. Based on polymorphisms in a 432-bp hypervariable region in the surface protective antigen A (spaA) gene, 34 isolates were classified into three groups: (i) Group 1 with methionine at position 203 (Met-203) and isoleucine at position 257 (Ile-257) (18 isolates of serotype 1a and one untypable isolate). (ii) Group 2 with Ile-257 (12 isolates of serotypes 1a, 1b, 2, 10 and 11), and (iii) Group 3 with alanine at position 195 (Ala-195) and Ile-257 (three isolates of serotype 1a). Isolates with Met-203 were highly pathogenic in mice and pigs, causing death in the pig and LD₅₀ values of 0.45–1.45 CFU per mouse. One live and three inactivated commercial E. rhusiopathiae vaccines were evaluated for efficacy against a Met-203 isolate. Almost all mice and pigs that received vaccine survived, while non-vaccinated controls all died within 5 days of the challenge. This indicates that swine erysipelas vaccines might be still effective in protecting animals against the recently prevalent Met-203 isolates in Japan.     

Dendritic cells in Leishmania infection

Dendritic cells (DCs) are key elements of the immune system, which function as sentinel in the periphery and alert T lymphocytes about the type of invading antigen and address their polarisation, in order to mount an efficacious immune response. Leishmania spp. are parasitic protozoa which may cause severe disease in humans and domestic animals. In this work, the main studies concerning the role of DCs in Leishmania infection are reviewed, in both the murine and human models. In particular, the importance of the genetic status of the hosts and of the different Leishmania species in modulating DC-mediated immune response is examined. In addition, different approaches of DC-based vaccination against experimental leishmaniasis, which could have important future applications, are summarised.     

浅谈WHO国家疫苗监管体系评估及其上市许可板块要求

通过卫生组织国家疫苗监管体系(National Regulatory Authority)评估是一个国家疫苗具备参与联合国全球采购资格的必要条件。本文对WHO国家疫苗监管体系评估整体加以简述,重点对上市许可板块指标进行归纳,通过探讨WHO国家疫苗监管体系评估上市许可部分的管理理念,以期为疫苗监管相关部门加强自身管理提升监管质量和效率有所提示。     

Vaccine demand driven by vaccine side effects: Dynamic implications for SIR diseases

For infections for which the perceived risk of serious disease is steadily low, the perceived risk of suffering some vaccine side effects might become the driving force of the vaccine demand. We investigate the dynamics of SIR infections in homogeneously mixing populations where the vaccine uptake is a decreasing function of the current (or past) incidence, or prevalence, of vaccine side effects. We define an appropriate model where vaccine side-effects are modelled as functions of the age since vaccination.It happens that the vaccine uptake follows its own dynamics independent of epidemiological variables. We show the conditions under which the vaccine uptake lands on a globally stable equilibrium, or steadily oscillates, and the implications of such behaviour for the dynamics of epidemiological variables. We finally report some unexpected scenarios caused by trends in vaccine side effects.     

Convincing the “Herd” of immunity: Lessons from smallpox vaccination in 19th century Germany

Although vaccination is a cost-effective way to control infectious diseases, it is often met with popular resistance. Studying smallpox in 19th century Germany, this paper explores how economic incentives contribute to this phenomenon. The paper adds to the literature by combining mathematical epidemiology and unpublished archival evidence from two German states - Baden and Wurttemberg. The two states are an intriguing case because their initial conditions and vaccination laws were similar. Despite this, Baden experienced lower smallpox prevalence and higher vaccination uptake than Wurttemberg. The epidemiological model predicts that incentives to vaccinate decline rapidly when immunization reduces prevalence. The archival evidence reveals that Baden offset this decline by creating a public vaccination system which reduced costs for vaccinees and vaccinators alike. This suggests that the high fixed costs of centralized immunization policies can be compensated by economies of scale and popular acceptance.