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Biomedical subjects

J E Banatvala

Publications and source records attributed to J E Banatvala.

At least 19 recordsLinked to original sources

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE: To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN: Randomised trial. SETTING: One London teaching hospital. SUBJECTS: 104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS: Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS: The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS: The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.

Adult

A lymphocyte transformation assay for the diagnosis of congenital rubella.

A rubella-specific lymphocyte transformation assay, using cryopreserved mononuclear cells, has been developed and used to evaluate specific responses among 21 children with congenitally acquired rubella (CAR), 25 healthy control children and 10 children with sensorineural deafness of unknown aetiology. Although all 21 children with CAR were seropositive, 12 (57.1%) failed to respond to rubella antigen in the transformation assay. Negative in vitro lymphocyte transformation responses were detected significantly more frequently among congenitally infected children below 3 years of age. Thirteen of the 25 (52%) control children were seropositive; only one of these seropositive children (7.6%) gave a negative transformation response. A negative rubella-specific lymphocyte transformation response in a seropositive child, particularly when aged 3 years or younger, is therefore suggestive of CAR. Four of the 10 children with deafness of unknown aetiology were rubella seropositive but gave negative responses in the transformation assay, suggesting that these children had CAR. Our assay may provide a very useful test for retrospective diagnosis of CAR, particularly in children under the age of 3.

Adult

Effect of hepatitis A vaccination schedules on immune response.

An inactivated hepatitis A vaccine was given to 104 seronegative volunteers aged between 19 and 60 years according to two schedules: 0, 1 and 2 months or 0, 1 and 6 months. The vaccine was well tolerated and 97 and 100% of vaccinees developed a serum antibody response following a single and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose; responses following the 0, 1, 6 month schedule were significantly higher at one year but, among those tested at two years, these differences were less marked. Vaccinees, when compared with naturally infected persons, developed poor or undetectable hepatitis-A-virus-specific immunoglobulin G and A antibody responses in saliva and parotid fluid. Such differences are, however, unlikely to affect the protective efficacy of the vaccine.

Adult

Rubella virus strains show no major antigenic differences.

To determine whether antigenic differences occur among rubella virus strains, five wild-type strains of rubella virus isolated in the UK, the USA, and in Japan between 1964 and 1987 and four attenuated vaccine strains were compared employing a panel of 28 monoclonal antibodies in neutralization, haemagglutination-inhibition, enzyme immunoassay, and indirect immunofluorescence assays. No antigenic differences were detected which confirms that rubella vaccines will protect against circulating strains and that rubella antigens used in serological tests for screening and diagnosis will detect antibodies induced by all strains.

Antibodies, Monoclonal

Hepatitis A.

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England

No association between islet cell antibodies and Coxsackie B, mumps, rubella and cytomegalovirus antibodies in non-diabetic individuals aged 7-19 years.

Viral antibodies were tested in a cohort of 44 islet-cell antibody-positive individuals age 7-19 years, and 44 of their islet cell antibody-negative age and sex-matched classmates selected from a population study of 4208 pupils who had been screened for islet cell antibodies. Anti-coxsackie B1-5 IgM responses were detected in 14 of 44 (32%) of the islet cell antibody-positive subjects and in 7 of 44 (16%) control subjects. This difference did not reach the level of statistical significance. None of the islet cell antibody-positive subjects had specific IgM antibodies to mumps, rubella, or cytomegalovirus. There was also no increase in the prevalence or the mean titres of anti-mumps-IgG or IgA and anti-cytomegalovirus-IgG in islet cell antibody-positive subjects compared to control subjects. These results do not suggest any association between islet cell antibodies, and possibly insulitis, with recent mumps, rubella or cytomegalovirus infection. Further studies are required to clarify the relationship between islet cell antibodies and coxsackie B virus infections.

Adolescent

Reactivity of enterovirus-specific IgM with infective and defective coxsackie B virions in patients with monotypic and multitypic IgM responses.

The antigenic specificity of enterovirus (EV)-specific IgM (EV-IgM) responses in patients with acute enterovirus infection was studied using an IgM-capture ELISA (EV-IgM ELISA) employing coxsackie B virus types 1-5 (CBV 1-5) antigens. Using antigens fractionated in caesium chloride (CsCl) gradients, and monoclonal antibodies (mAbs) and polyclonal antisera of defined specificity as detector antibody to detect IgM-bound antigen, IgM of single serotype specificity was shown to react consistently with dense, infective virions. When responses were directed against multiple CBV serotypes, IgM reacted consistently with lighter, defective virions. Serotype-specific mAbs and polyclonal antisera reacted with a range of determinants, some present only on infective virions, some only on defective virions, and others which were common to both types of virion. Common EV group determinants were confined to defective virions. Neither infective nor defective virions of any one serotype reacted with IgM from all patients with EV infection. An assay capable of detecting EV-IgM in all EV infections will require an antigen cocktail incorporating a wide range of determinants, rather than a single group EV antigen.

Animals

Rubella vaccines.

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Antibodies, Viral

Liver disease among homosexual males.

5% of 2612 homosexual males attending genitourinary clinics were found to be hepatitis-B surface-antigen (HBsAg) positive. Liver biopsy was done in 25 who had abnormal liver-function tests but no symptoms or signs of liver disease, and 14 (56%) of these proved to have chronic active hepatitis or active cirrhosis. Neither the liver-function tests nor the viral markers in serum reflected the severity of the liver disease. 38% of a group of 118 HBsAg positive patients were HBeAg positive, and sexual contacts of these individuals may be at serious risk of infection.

Carrier State

HLA antigens and responses to rubella vaccination.

Attempts were made to correlate virus excretion, joint symptoms and antibody response with human leukocyte antigens (HLA) in seronegative adult women given attenuated rubella vaccine. No association was shown between HLA antigens of the A and B loci and excretion of either high or low titres of RA27/3 vaccine among 26 volunteers. However, virus excretion was influenced by such factors as the time of day at which specimens were collected and the method of virus isolation. Our study therefore failed to confirm the hypothesis that certain persons are good 'spreaders' of rubella virus and that this capacity is associated with HLA-A1 and B8. The study of joint symptoms following vaccination with Cendehill, HPV77.DE-5, RA27/3 or To-336 vaccines showed no association between such symptoms and HLA antigens. However, joint symptoms occurred within 7 days of the onset of menstruation in 33 of 47 (70%) vaccinees (P less than 0.01) and it is therefore suggested that hormonal factors must play a role. No association between HLA antigens and haemagglutination inhibition (HAI) antibody titres, 8 weeks after vaccination with RA27/3, was found amongst 34 volunteers.

Adult

Maternal rubella at St. Thomas' Hospital: is there a need to change British vaccination policy?

During the 28 weeks starting April 3, 1978, 269 pregnant women were assessed serologically because of exposure to or development of rubella-like illnesses, this number being four times greater than that during either of the previous 2 years. Only 33 (12%) of these patients had previously been given rubella vaccine. Rubella was confirmed serologically in 17 patients; among patients attending antenatal clinics the overall risk of acquiring infection was about 1 in 155. The mean age of patients acquiring maternal rubella was 27.9 years, and all but 1 had left school before the rubella vaccination programme started. 55 (92%) of 60 household contacts were children, of whom 24 (40%) were of preschool age and 13 (21.7%) aged less than 2 years. The interval between contact and presentation for serological studies was often long and, because of this, 79 sera had to be tested for virus-specific IgM. No drastic change in rubella vaccination policy is required but there should be more emphasis on vaccination of women of childbearing age.

Adolescent