Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis.

Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.

An evaluation of adverse events following an immunization campaign with the live, attenuated SA14-14-2 Japanese encephalitis vaccine in Cambodia.

INTRODUCTION: Japanese encephalitis (JE) virus is the most common cause of vaccine-preventable encephalitis in Asia. The SA14-14-2 JE vaccine manufactured by Chengdu Institute of Biological Products has been shown to be safe and effective in clinical trials and childhood routine immunization programs. However, there are few published reports describing results of surveillance for adverse events following immunization (AEFI) when the vaccine is used in mass campaigns. We describe the results of AEFI surveillance following a 2013 vaccination campaign among almost 310,000 children aged 9 months-12 years in Battambang Province, Cambodia. METHODS: Routine AEFI surveillance was strengthened by staff training and supplemented by active hospital surveillance. An AEFI was defined as any sign, symptom, or disease temporally associated (i.e., within 4 weeks) with receipt of the vaccine, irrespective of whether it was considered related to immunization. Data were collected on standardized forms and causality assessments were conducted for serious AEFI. RESULTS: Passive and active surveillance detected 28 AEFI for an overall incidence of 9.0 AEFI per 100,000 doses administered. The most frequent events were vasovagal episodes (n = 7, 25%) and rash (n = 6, 21%), and most other events were common childhood conditions such as fever and vomiting. Three AEFI were classified as serious, including one hypersensitivity reaction and two meningoencephalitis cases. Of these, the hypersensitivity event was the only serious AEFI classified as being consistent with a causal association to immunization. CONCLUSIONS: Most reported adverse events were conditions that commonly occur after other childhood vaccinations or independently of vaccination, and in the context of careful monitoring for serious AEFI only one serious event consistent with a causal association with immunization was identified. These results support the good safety profile of the SA14-14-2 JE vaccine, and provide reassuring data as the vaccine's use expands.

Nicotinic attenuation of central nervous system inflammation and autoimmunity.

The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells. In the CNS, nicotine exposure selectively reduces numbers of CD11c(+) dendritic and CD11b(+) infiltrating monocytes and resident microglial cells and down-regulates the expression of MHC class II, CD80, and CD86 molecules on these cells. The results underscore roles of nicotinic acetylcholine receptors and nicotinic cholinergic signaling in inflammatory and immune responses and suggest novel therapeutic options for the treatment of inflammatory and autoimmune disorders, including those that affect the CNS.

[Yellow fever vaccination in non-immunocompetent patients]. / Vaccination contre la fièvre jaune en dehors des sujets immunocompétents.

Any person travelling in countries where yellow fever (YF) is endemic and without presenting contra-indication for the vaccination against YF may be vaccinated. This vaccination can very rarely induce a potentially lethal neurotropic or viscerotropic disease. In severely immunodeficient patients, the vaccination is contra-indicated because postvaccinal encephalitis may occur after the vaccination, due to vaccine strain pathogenecity. It is important to evaluate the general health status in elderly individuals before vaccinating because of the increased risk of viscerotropic disease in people of 60 years of age and over. Pregnant women should not be vaccinated, except if departure to an endemic zone is unavoidable. YF vaccinatio is contra-indicated for newborns under six months of age. Solid organ grafts, congenital immunodeficiency, leukemia, lymphoma, cancer, and immunosuppressive treatments are contra-indications for this vaccination. Nevertheless, YF immunization is possible after a bone marrow graft and a two-year period without graft-versus-host disease or immunosuppressive treatment. There is no data to support that immunization of the dono prior to the graft could confer protection against yellow fever to the recipient. Low doses, short courses of corticosteroids either as systemic treatment or intra-articular injections are not contra-indications for YF vaccination. Patients infected with HIV with stable clinical status and T CD4-cel count above 200 cells per millimetre cube may be vaccinated. Thymic diseases, including thymoma and thymectomy, are contra-indications for YF vaccination. Finally, a substantial residual level of antibodies beyond 10 years after the latest vaccination could confer protection, thus avoiding a new vaccination when it is an issue.

[Evaluation of mouse brain-derived, inactivated Japanese encephalitis vaccine].

Japanese encephalitis (JE) is a serious encephalitis caused by JE virus. Approximately 20% of JE patients die and 50% patients recover with neuro-psychiatric sequelae. In Japan, the number of JE patients was over 1000 per year in 1960s; however, the number decreased dramatically and has been less than 10 since 1990. Ministry of Health, Labour and Welfare suspended the strong recommendation for vaccination with the mouse brain-derived JE vaccine, because of cases who developed acute disseminated encephalomyelitis (ADEM) after vaccination with JE vaccine. However, it has not been fully confirmed on scientific bases that ADEM was caused by mouse brain-derived JE vaccine. Tissue culture derived-JE vaccine is under development. It is expected that this new vaccine will come to the market soon and that the recommendation of universal vaccination with JE vaccine will be implemented at the earliest occasion.

Virus and Immune-Mediated Encephalitides: Epidemiology, Diagnosis, Treatment, and Prevention.

Virus encephalitis remains a major cause of acute neurological dysfunction and permanent disability among children worldwide. Although some disorders, such as measles encephalomyelitis, subacute sclerosing panencephalitis, and varicella-zoster virus-associated neurological conditions, have largely disappeared in resource-rich regions because of widespread immunization programs, other disorders, such as herpes simplex virus encephalitis, West Nile virus-associated neuroinvasive disease, and nonpolio enterovirus-induced disorders of the nervous system, cannot be prevented. Moreover, emerging viral disorders pose new, potential threats to the child's nervous system. This review summarizes current information regarding the epidemiology of virus encephalitis, the diagnostic methods available to detect central nervous system infection and identify viral pathogens, and the available treatments. The review also describes immune-mediated disorders, including acute disseminated encephalomyelitis and N-methyl-D-aspartate receptor antibody encephalitis, conditions that mimic virus encephalitis and account for a substantial proportion of childhood encephalitis.

[Physiopathology of pertussis encephalopathy. Prophylaxis. Pathogenesis of the "reaction" against intramuscular pertussis vaccine. Vaccination with "shield"]. / Fisiopatologia dell'encefalopatia pertussica. Profilassi. Patogenesi delle "reazioni" da vaccino antipertosse intramuscolo. Vaccinazione con "copertura".

The specific local and humoral immunological situation of the child, by permitting or not (+/- specific IgA-S) the passage of the Bordetella toxins to the bloodstream and the formation or not (+/- specific circulating IgG) of Circulating Immune Complexes (CIC), brings back to Type III Immunoreactions the pathogenesis of the pertussis encephalopathy and the reactions provoked by intramuscular vaccine. Since the antihistaminics and antiserotoninics can prevent the CIC precipitation, the Author believes that this would imply the indication to the usage of antihistaminics or antiserotoninics to prevent bot the neurologic complications of the illness and the systemic reactions to the intramuscular vaccine.

[Prevention of complications of smallpox vaccination]. / O profilaktike postvaktsinal'nykh oslozhneii posle privivok protiv natural'noi ospy.

In observance of the rules of vaccination and unfavourable anamnesis in the vaccinated serve as the main causes of postvaccinal complications (30 and 22%, respectively). The great majority of complications occurs at the age of 1 to 3 years (76%). In 94% of cases complications are recorded in primarily vaccinated individuals. Solution of such problems as introduction into wide practice of sparing methods of immunization and special scheme of preliminary preparation to the vaccination of weak children and those with conditioned contraindications is necessary for the purpose of prevention of complications; a possibility of using, along with gamma-globulin, of synthetic preparations, and of subjecting older children to primary vaccination for prevention of complications is discussed.

[Present and future of oral pertussis vaccination]. / Gegenwart und Zukunft der oralen Pertussis-Schutzimpfung.

Parenteral immunization against whooping cough shows some disadvantages which led to proposals to curtail pertussis vaccination in some countries. As a result a striking rise in pertussis morbidity in these regions was noted, so vaccination against whooping cough is still indicated. We developed an oral vaccine for the neonate to achieve a protective immunity at a time when it is especially needed and to avoid side-reactions. Oral vaccine was given to more than 15,000 newborns, vaccination results of the last 3 years are reported.

[Smallpox vaccine, then and now. From the "cow lymphe" to the cell-culture vaccine]. / Pocken-Impfstoff, einst und jetzt. Von der "Kuhlymphe" zur Zellkultur-Vakzine

There have been few changes in the preparation of smallpox vaccine since Eduard Jenner described his method of preventive inoculation in 1798. Jenner's vaccine, "the matter", was maintained in man by arm to arm passage. The only major achievement in production methods was the introduction of an animal host for virus propagation. The skin of living calves or sheep was inoculated with seed virus and the "pulp" harvested three to four days later. The disadvantages of this procedure are evident: massive bacterial contamination in spite of rigorous cleanliness and excessive amounts of undesired tissue debris in the crude material to be used for vaccine production. In spite of these obvious disadvantages the method is still in use all over the world. Advances in tissue culture techniques have led to the production of all modern vaccines for use in animals and in the human from this substrate with low initial content of foreign protein and of primary sterility. The only exception today is conventional smallpox vaccine. Sporadic attempts to produce smallpox vaccine in tissue culture have been recently and successfully made in England, Holland and Yugoslavia. The Bavarian State Institute of Vaccination has adopted Vaccinia strain Elstree to primary cultures of chick embryo fibroblasts. The virus propagation in roller bottles permits the economical production of a high titered vaccine with a stability equal to that of calf origin. The cell culture harvest is bacteriologically steril and has a minimal content of foreign protein. Within the past two years this cell culture vaccine has totally replaced the old "calf lymph". Vaccination takes are equal, complications have so far not come to our attention.

[Utilization of the MVA-immunization schedule from the view point of the public health service]. / Zur Anwendung der MVA-Stufenimpfung aus der Sicht des öffentlichen Gesundheitsdienstes.

The world-wide smallpox eradication program sponsored by the WHO has been successful. Furthermore the legislation regarding smallpox vaccination in the Federal Republic of Germany has been given a new form. The place of the previous mass-vaccination has been taken by vaccination of individuals. Under this aspect safe procedures for vaccination are required. Any vaccination used by Public Health Service has to fulfill the following criteria: High protection against the disease without adverse side-effects or risks; it should be simple to administer and applicable under ordinary circumstances. For primary vaccination against smallpox the MVA-vaccination meets these demands entirely. It is reported about own experiences with 700 vaccinations using the attenuated virus "MVA"; complete documentation is given. Not a single complication nor any adverse side-effects have been seen. The Public Health Service has gained great experience in the field of vaccination. It is responsible for the protection of the individual as well as the public, as it is undesirable that there develops and unvaccinated group within the population. The individual claim a complete protection through vaccination which should be absolutely free of any risk.

[Problems of prevention, registration and evaluation of post-vaccination neurogenic lesions in children from clinical and legal viewpoints. II. Problems in the evaluation of neurogenic post-vaccination lesions in childhood]. / Zur Problematik der Verhütung, Erfassung und Begutachtung von neurogenen Impfschäden im Kindesalter aus klinischer und rechtlicher Sicht. II. Mitteilung: Probleme der Begutachtung von neurogenen Impfschäden im Kindesalter

On the view of neurologist the authors describe the suppositions and the special problems of diagnostic and the importance of clinical and paraclinical findings for medical vaccination reports. They examined 13 patients with neurological cerebral defects after triple vaccination (DPT).

[The development of vaccination as demonstrated on the development of the Bavarian State Vaccination Institute in the 19th and 20th centuries]. / Zur Entwicklung der Schutzimpfung aufgezeigt an der Entwicklung der Bayerischen Landesimpfanstalt im 19. und 20. Jahrhundert

In 1801 the smallpox vaccination has been introduced in Bavaria by order of the Duke Franz Joseph. He appointed a Medical Superintendent, responsible for smallpox vaccinations for the whole country. This was the hour of birth for the Institute, too. The Institute developed quickly to a point of crystallization in the field of prophylactic medicine, research on infectious diseases and social pediatrics. By this Institute the "Retrovaccine" against smallpox was introduced 1856. 1967 -- 1976 an attenuated life smallpox-vaccine (MVA) has been developed. Some years ago the activities of the Institute had been focussed into research of complications after vaccinations and up to date, on the pathogenesis of Multiple Sclerosis. A historical review demonstrates the development of the Institute in the past up to modern activities in research, teaching students and postgraduate education and in medical practice.

The smallpox vaccine and postvaccinal encephalitis.

Smallpox is one of the deadliest infectious diseases in history. The discovery by Edward Jenner that inoculation with a droplet of pus from a cow with cowpox protected a person from smallpox resulted in the successful vaccination of millions of people. There were, however, complications associated with smallpox vaccination; the most serious complication was postvaccinal encephalitis, which was reported to occur with an incidence of 1 in 110,000 vaccinations and a case-fatality rate of 50%. Before we become complacent with the idea that we will respond to a bioterrorism attack with a mass immunization program for smallpox, it is important to be reminded of the risk and clinical manifestations of postvaccinal encephalitis and the efficacy of antivaccinia gamma-globulin in preventing this complication. The first case of postvaccinal encephalitis as a complication of the Jennerian cowpox inoculation was observed in 1905. A century later, there is no effective therapy.