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Restoration of complement-enhanced neutralization of vaccinia virus virions by novel monoclonal antibodies raised against the vaccinia virus complement control protein.

The vaccinia virus complement control protein (VCP) is secreted by infected cells and has been shown to inhibit complement activation through interactions with C3b/C4b. It contains four short consensus repeat (SCR) domains. It has been suggested that all four SCRs are required for VCP's activity. To elucidate which SCR domains are involved in abolishing complement-enhanced neutralization of vaccinia virus virions, we generated and characterized a panel of mouse monoclonal antibodies (MAbs) raised against VCP. Ten MAbs were isolated and all recognized VCP on Western blots under reducing conditions as well as native-bound VCP in a sandwich enzyme-linked immunosorbent assay. Three of the 10 MAbs (2E5, 3D1, and 3F11) inhibited VCP's abolition of complement-enhanced neutralization of vaccinia virus virions. These MAbs blocked the interaction of VCP with C3b/C4b. The seven remaining MAbs did not alter VCP function in the complement neutralization assay and recognized VCP bound to C3b/C4b. To understand MAb specificity and mode of interaction with VCP, we mapped the MAb binding regions on VCP. The seven nonblocking MAbs all bound to the first SCR of VCP. One of the blocking MAbs recognized SCR 2 while the other two recognized either SCR 4 or the junction between SCRs 3 and 4, indicating that structural elements involved in the interaction of VCP with C3b/C4b are located within SCR domains 2 and 3 and 4. These anti-VCP MAbs may have clinical significance as therapeutic inhibitors of VCP's complement control activity and may also offer a novel approach to managing vaccinia virus vaccine complications that occur from smallpox vaccination.

Animals↗

New Principles of Development of Preparations for Immunoprophylaxis.

In the development of new vaccine the fate of preparation depends on three main factors: potential to decrease morbidity and benefits from vaccine use; the risk of post vaccinal complications and possible damage from vaccination; the cost of vaccine and economic advantages. By basic parameters, dealing with safety and effectiveness, home immunological preparations, first of all vaccines used in framework of vaccination calendar, meet all the requirements of WHO. However, absolutely safe vaccines don't exist in the world. All the above may be an evidence of the need to find new approaches to the development of more improved vaccines. Gene-engineering technology is a revolutionary event in vaccinology, it made it possible to develop recombinant vaccines, possessing weak reactogenity and sufficient effectivity. Anti-idiotypic vaccines didn't go out the sphere of experimental approaches. Any protein vaccine, being introduced to the body, is undergone to digestion. Forming peptides interact with histocompatibility antigens and acquire immunogenic properties. The development of new class vaccines is based on this principle. Synthetic peptide vaccines are safe and low reactogenic. In spite of a large amount of experimental peptide vaccines, there is no still any vaccine of such a type in the practice of health services. Meanwhile, WHO gave recommendations dealing with development and control of peptide vaccines, suggesting that such vaccines will appear in the next future. The same recommendations were given for so called DNA vaccines.

Journal Article↗

Ocular complications of smallpox vaccination.

PURPOSE: To describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options. DESIGN: Review of pertinent medical literature and recent treatment recommendations of the Centers for Disease Control and Prevention. RESULTS: After immunization against smallpox, vaccinia infection of the eyelid, conjunctiva, or ocular surface can result from accidental autoinoculation from a vaccination site before scab formation or from contact with a recently vaccinated individual. While uncommon, corneal involvement can lead to stromal opacification and scarring. Clinical findings of ocular and periocular vaccinia must be differentiated from those produced by other pathogens such as molluscum contagiosum, herpes simplex, varicella zoster, and acanthamoeba infections. Clinical diagnosis can be confirmed by electron microscopy to identify the presence of orthopoxvirus, as well as by virologic culture, polymerase chain reaction, and/or restriction endonuclease analysis of viral isolates. CONCLUSIONS: While the majority of ocular complications of smallpox vaccination in immunocompetent patients are self-limiting, selective cases may require treatment with trifluridine drops, topical corticosteroids and vaccinia immune globulin (VIG). Vaccinia virus does not appear to be sensitive to acyclovir. Specific treatment recommendations are outlined for the spectrum of ocular manifestations.

Centers for Disease Control and Prevention, U.S.↗

Neurological complications following measles vaccination.

In Hamburg 18 cases of neurological complications following vaccination with live measles virus vaccine (including 2 cases of abortive encephalopathy) have been observed between 1971--1978. A causal connection was assumed in 14 cases, that means an incidence of 1 neurological complication per 2,500 vaccinees and an incidence of 1 abortive encephalopathy per 17,650 vaccinees. These results differ from studies of various countries which used the same vaccine strain (Schwarz). Clinical symptoms, age distribution and incubation period are demonstrated. The prognosis seems to be good; the risk of vaccination compared to the risk following original measles is between 1:10 (convulsions) and 1:18 (encephalopathy).

Brain Diseases↗

[Complications of BCG vaccine].

The different types of complications encountered with the application of BCG vaccine are described together with a scheme of its characteristics and application techniques. The use of oral vaccine is discarded. The normal and the different abnormal reactions are described; likewise, atypical localizations and all their consequences. Finally, pertinent recommendations for the application of this vaccine are made.

Administration, Oral↗

Danger of sunburn following vaccination.

The complications of smallpox vaccination are reviewed. A case of disseminated vaccinia is presented. It is suggested that patients with sunburn may be susceptible to the complications of smallpox vaccination.

Child, Preschool↗

[Findings on the occurrence of complications caused by DEV and HDVC (delta) vaccines].

The complications arising from two different anti-rabies vaccines were compared: DEV (duck embryo vaccine; the schedule included 14 daily doses plus 3 boosters) and HDCV (human diploid cells vaccine; the schedule included 5 doses plus 1 booster). 2646 patients were immunised, following a post-exposure prophylaxis, at the Antirabies Unit of the Institute of Hygiene of Rome. Among the 1434 patients immunised with DEV, 364 (25.38%) developed side-effects, whilst among the 1212 subjects immunised with HDCV only 47 (3.88%) developed side-effects. Using DEV the more frequent complications were as follows: fever (48.62%), regional adenopathy (49.45%), erythema (89.29%), local induration (41.48%). Using HDCV the main complication was fever (65.96%). The principal association of complication in DEV were: erythema + induration + edema + adenopathy + fever; general malaise + asthenia + adenopathy; dizziness + headache. Hyperthermia resulted often associated with regional adenopathy and the general malaise with the headache in the vaccinated with HDCV. All complications were widely distributed during the period of immunisation. However most side-effects arose following the 5th DEV dose or the 2nd HDCV dose. Regional adenopathy, was the more persistent and less tolerated symptom, also local erythema showed a long persistence, whilst the other symptoms regressed within 48-72 hours with proper therapy and rest. Sex and age did not influence the incidence nor the type of complications. Neither neuroparalysis was detected nor serious impairment of health. In our study the coincidence of unwanted effects, following an antirabies immunisation, seems lower than that described in the literature. This was probably due to the high level of purification of the vaccine and possibly to the different recording of the minor symptoms.

Drug Eruptions↗

Neurologic complications of immunizations.

Although there does appear to be at least a temporal relationship between pertussis immunization and serious acute neurologic illness, data to suggest that children with stable preexisting neurologic disease or positive family history of neurologic disease are at increased risk for complications of pertussis immunizations are inconclusive. Furthermore, there are no firm statistical data concerning the incidence of pertussis vaccine-related encephalopathy. Rather, the literature on pertussis vaccine complications is replete with anecdotal reports and retrospective studies with a number of questionable conclusions drawn from this inadequate data base. Unfortunately, these conclusions have been sensationalized and exploited with litigious fervor to the point that the practice of pertussis immunization is being questioned in the United States. A number of points should be reiterated: pertussis is a dangerous and deadly disease, as seen in the epidemic in Great Britain; pertussis immunization is effective in protecting against the disease; and there is no conclusive proof that the incidence of complications from pertussis vaccination of children with seizure disorders or other preexisting stable neurologic abnormalities is higher, because appropriate studies have not been done to define such a risk. We would do well to keep these facts in mind in order to avoid a disaster similar to the pertussis epidemic in Great Britain. Pertussis vaccination should be given to all children except those with allergic hypersensitivity, a progressive neurologic disorder, or an adverse reaction to a previous pertussis dose.

Adolescent↗

Smallpox vaccination reactions, prophylaxis, and therapy of complications.

Smallpox vaccination in the United States is a routine public health measure which has been under intensive review during the last decade. The most frequently occurring adverse reactions to vaccination are benign and require little or no systemic therapy. These reactions include accidental infection, erythematous and urticarial rash, and generalized vaccinia. Chickenpox occurring concurrently with vaccination presents no problem unless vaccinia has widely superinfected the chickenpox lesions. There is no risk to the pregnant woman who is vaccinated, but there is a slight risk that the fetus will develop fetal vaccinia. The vaccinia does not cause congenital malformations. Vaccinia hyperimmune globulin (VIG) in prophylactic dosage may be given to a pregnant woman who is traveling to a smallpox infected or endemic area in order to prevent fetal vaccinia. Vaccinia necrosum and eczema vaccinatum require vigorous systemic therapy with VIG, and often thiosemicarbazone. Post-vaccinial encephalitis, while frequently serious, has not been shown to be ameliorated by VIG therapy, although there are data which suggest VIG has some value in prophylaxis for encephalitis. Prophylaxis, prompt recognition, and proper therapy may reduce the fatality rates of these complications. Revaccination of patients who have suffered a complication is a frequent clinical problem. Revaccination of an individual who has had post-vaccinial encephalitis or vaccinia necrosum is contraindicated unless the risk of contracting smallpox outweighs the risk of the above two diseases. Revaccination of children who have had eczema vaccinatum is not contraindicated. Revaccination of children with a history of accidental infection or erythematous or urticarial rash presents no known or theoretically increased risk.

Eczema↗

Lymphadenitis as a late complication of BCG vaccination.

Lymphadenitis is a relatively common complication following intradermal BCG vaccination, and usually occurs 6 to 9 months after injection. However, lymphadenitis following BCG given by the scarification method is rare. We report a case of BCG lymphadenitis occurring 11 and 18 years after vaccination by the scarification method.

BCG Vaccine↗

Avian infectious bronchitis virus.

Infectious bronchitis virus (IBV) is prevalent in all countries with an intensive poultry industry, with the incidence of infection approaching 100% in most locations. Vaccination is only partially successful due to the continual emergence of antigenic variants. At many sites, multiple antigenic types are simultaneously present, requiring the application of multiple vaccines. Although many countries share some common antigenic types, IBV strains within a geographic region are unique and distinct, examples are Europe, the United States of America and Australia. Measures to restrict the introduction of exotic IBV strains should therefore be considered. Infectious bronchitis has a significant economic impact; in broilers, production losses are due to poor weight gains, condemnation at processing and mortality, whilst in laying birds, losses are due to suboptimal egg production and downgrading of eggs. Chickens and commercially reared pheasants are the only natural hosts for IBV. Other species are not considered as reservoirs of IBV. The majority of IBV strains cause tracheal lesions and respiratory disease with low mortality due to secondary bacterial infections, primarily in broilers. Nephropathogenic strains, in addition to tracheal lesions, also induce prominent kidney lesions with mortality of up to 25% in broilers. Strains of both pathotypes infect adult birds and affect egg production and egg quality to a variable degree. Infected chicks are the major source of virus in the environment. Contaminated equipment and material are a potential source for indirect transmission over large distances. Virus is present in considerable titres in tracheal mucus and in faeces in the acute and recovery phases of disease, respectively. Virus spreads horizontally by aerosol (inhalation) or ingestion of faeces or contaminated feed or water. The virus is highly infectious. Clinical signs will develop in contact chicks within 36 h and in nearby sheds within one to two days. Infection is resolved within fourteen days with a rise in antibody titres. In a small number of chicks, latent infection is established with subsequent erratic shedding of virus for a prolonged period of time via both faeces and aerosol. Movement of live birds should be considered as a potential source for the introduction of IBV. Isolation and identification of IBV is needed for positive diagnosis. The preferred method of isolation is to passage a sample in embryonating specified-pathogen-free chicken eggs. Identification is either by monoclonal antibody based enzyme-linked immunosorbent assay (ELISA) or polymerase chain reaction. Virus neutralisation test in tracheal organ culture is the best method for antigenic typing. Continual use of live vaccines complicates diagnosis since no simple diagnostic tool can differentiate a field from a vaccine strain. Nucleotide sequencing of the S1 glycoprotein is the only method to discriminate between all IBV strains. Serology is also complicated by continual use of live vaccines. For surveillance purposes, ELISA is the method of choice, regardless of the antigenic type of IBV involved. The assay is used to monitor the response to vaccination, but field challenge can only be detected if flock antibody status is monitored continually. The antigenic type of a challenge strain involved cannot be ascertained by ELISA.

Animals↗

[Complications after BCG vaccination in the urban section of Lodź in the years 1994-5].

The purpose of this paper was to evaluate the incidence of complications after BCG vaccination in children from urban area of Lódź in 1994-1995 and to give their pathological and prognostic interpretation on the basis of immunological and Groër allergometric examinations. The obtained data demonstrate that postvaccinal complications occurred in 46 children, that is 0.7/1000 of vaccinated population. They were observed mainly in newborns (45.7%), whereas they were particularly rare in revaccinated six-year-old children (13%) and schoolchildren (8.7%). In half of the cases there was an evidence of ulceration and suppuration in the site of vaccination, in another half--suppuration of local lymph nodes with or without fistula. Immunological and allergometric examinations were carried out in 21 children with post-vaccinal complications and 21 children with normal post-vaccinal period. In both groups the following were the subjects of evaluation: values of B and T lymphocytes and their CD4 and CD8 subpopulations, lymphocytes proliferative response to mitogenic PHA doses and tuberculin, as well as IgG, IgA and IgM levels. Immunological and allergometric examinations indicated that immunosuppression was neither the cause nor the effect of BCG complications.

Adolescent↗