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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

Prevalence of hepatitis C in tropical communities: the importance of confirmatory assays.

The prevalence of antibody to hepatitis C virus (HCV) was estimated in 3 tropical populations using 2 screening ELISAs to detect antibody to the c100-3 antigen and 2 supplementary assays designed to test the specificity of these tests. Two hundred and eighty-six of 385 (74.2%) sera from Kiribati, 17 of 138 (12.3%) sera from Vanuatu, and 39 of 173 (22.5%) sera from Zaire were reactive in the initial screening assay. The proportion of reactive sera which were also reactive in the second screening ELISA varied between populations (55.1% in Kiribati, 85.1% in Vanuatu, and 39.2% from Zaire). Reactive sera were selected at random for confirmatory testing. Only 3 of 49 (6.12%) of sera from Kiribati and 1 of 14 (4.76%) of sera from Vanuatu positive in the initial ELISA were reactive in the confirmatory assays. The proportion of confirmed positive sera from Zaire was higher 8 of 28 (28.5%). Based on the results of these supplementary assays the estimated prevalence of anti-HCV in these populations is 4.8% in Kiribati, less than 1% in Vanuatu, and 6.4% in Zaire. Reliance on a single screening ELISA to estimate the prevalence of anti-HCV in stored sera from tropical communities may lead to a gross over-estimate of the true prevalence in these populations.

Antibody Specificity

Quantitation of HIV: correlation with clinical, virological, and immunological status.

A quantitative assay has been used to measure titres of infectious HIV in peripheral blood of symptomatic and asymptomatic patients. Viral titres were assessed in conjunction with virological and immunological status of patients including measurement of p24 antigen, antibody responses to structural (gp41, p24) and regulatory gene products (NEF, REV, TAT, and VIF), determination of beta 2 microglobulin levels and enumeration of lymphocyte subsets. Titres of HIV were significantly higher among symptomatic than asymptomatic patients. Viral load was closely associated with the number of CD4+ cells, the proportion of these cells harbouring HIV increasing with disease progression. Higher titres of infectious HIV among symptomatic patients was also associated with p24 antigenaemia and decreased antibody responses to NEF.

AIDS-Related Complex

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

HIV excretion patterns and specific antibody responses in body fluids.

HIV excretion patterns and specific antibody responses were evaluated in blood, semen, female genital secretions, saliva, and crevicular fluid. Samples were examined for infectious virus, viral antigens, viral nucleic acid, HIV specific IgG, IgA, anti-nef, and anti-p24. Viral load in peripheral blood appeared to increase with disease progression. The proportion of patients with antibody responses specific for nef and p24 was also lower among patients with more advanced disease. Infectious virus and viral antigens were detected infrequently and at lower levels in body fluids than in blood, which may reflect the presence of local antibodies. HIV nucleic acid was detected in some semen and saliva samples in the absence of infectious virus.

Female

Enterovirus-specific serum IgA antibody responses in patients with acute infections, chronic cardiac disease, and recently diagnosed insulin-dependent diabetes mellitus.

Employing an antibody class capture ELISA, we assessed the significance of enterovirus (EV)-specific serum IgA (EV-IgA) as a marker of EV infection. EV-IgA was detectable in 64% of sera from patients with acute illnesses which may be attributable to EV infection who also had EV-IgM, but also in 30% of sera from patients without evidence of EV infection. High EV-IgA levels were more closely associated with the presence of EV-IgM and were demonstrable in 39% of patients with acute infections who were EV-IgM positive, compared to 3% of those who were EV-IgM negative. Among patients with acute EV infection confirmed by virus isolation, EV-IgA was present in 67% and EV-IgM was present in 83%. As a marker of acute EV infection, EV-IgA is less sensitive and less specific than EV-IgM. EV-IgA responses in patients with chronic cardiac disease paralleled EV-IgM responses in some cases but there was no significant association between these two antibody responses in this group as a whole. High EV-IgA responses were present in 20% of EV-IgM positive and 21% of EV-IgM negative patients, and may persist as a result of an immunoregulatory defect leading to virus or antigen persistence at mucosal surfaces. High EV-IgA levels were also detectable in 33% of EV-IgM positive newly diagnosed insulin-dependent diabetics but in none who were EV-IgM negative, which suggests that most EV infections in these patient were acute rather than persistent.

Acute Disease

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

Fetal infection after maternal reinfection with rubella: criteria for defining reinfection.

Five cases of asymptomatic maternal reinfection with rubella are described that occurred in England and Wales during 1985-8 and resulted in intrauterine infection. The criteria for diagnosing reinfection are described. In four cases the rubella contact was with the woman's own children. Two women had therapeutic abortions, rubella virus being recovered from the products of conception, and three were delivered of infants with congenitally acquired disease. Though the risks associated with maternal reinfection with rubella are very small and being measured in a prospective study, it is hoped that the recently introduced augmented programme of rubella vaccination will reduce rubella in the community and therefore this small risk still further.

Female