Absence of cell-mediated immunity to rubella virus 5 years after rubella vaccination.

The long-term effectiveness of rubella vaccination in childhood is particularly important because the ultimate goal of immunization is the prevention of infection during pregnancy. Of 25 healthy children tested 4 to 5 years after rubella vaccination, 19 showed no evidence of cell-mediated immunity (CM) to rubella virus despite the presence of hemagglutination-inhibition or complement-fixation antibodies or both. Twenty-two of 25 seropositive, naturally infected young adults showed evidence of CMI. These results indicate that fetuses of women who have been vaccinated against rubella may not be protected against damage by wild rubella infection during the pregnancy, when CMI is physiologically depressed.     

Surveillance of antibody to measles,mumps, and rubella by age.

Before the introduction of measles, mumps, and rubella vaccine a survey was carried out to measure antibody prevalence to the three viruses by age. A total of 8716 samples of serum collected by five public health laboratories in different parts of England during 1986-7 were tested. Despite the current measles vaccination programme 60% of children aged 1-2 years did not have measles antibody and over 80% did not have antibodies to mumps and rubella. In the 3-4 year age group 17% of the children were susceptible to measles, 55% to mumps, and 73% to rubella. The results suggest that vaccinating children early in the second year of life will be necessary to eliminate the three diseases. The survey provides baseline data for continuing surveillance of the immediate and long term effects of the new vaccination strategy.     

Avidity of immunoglobulin G to rubella virus in post-vaccination and post-infection immunity

Comparative evaluation of avidity of IgG to rubella virus in vaccinated persons, in patients with rubella or other exanthematous illness, and in healthy persons revealed similar patterns in post-vaccination and post-infection immunity. Virus specific low avidity IgG (index of avidity < or =30%) were detected in patients with rubella during 7 weeks after symptoms appeared as well as in vaccinated persons which were tested 6 weeks after vaccination. Low avidity antibodies in sera were detected in 96% of patients with rubella and in 75% of vaccinated persons which were not immune before immunization. Live attenuated vaccines Ervevax, Priorix, and MMR-II had similar ability to induce low avidity IgG to rubella virus. Increase of low avidity antibodies concentration was noted after immunization of children with low levels of antibodies before vaccination. After immunization of persons with high avidity antibodies in serum, index of avidity remained above threshold. Anamnestic high avidity IgG (index of avidity 51-100%) were detected in majority of immune healthy persons (96.4%) as well as in patients with exanthematous illnesses not related to rubella infection (93.6%). ELISA test-systems for detection of low avidity IgG to rubella virus allow to obtain reliable information about seroconversion rate and characteristics of immune response in vaccines. Detection of low avidity IgG in serum obtained 5-6 weeks after immunization points to primary immune response, whereas identification of high avidity antibodies reveals already immune persons.     

Mitotic exit: closing the gap

Completion of mitosis is triggered by the activation of the Ras-like GTP-binding protein Tem1p. In the November 30, 2001 issue of Cell, Hu et al. suggest that Tem1p activation is achieved by inhibition of its two-component GAP Bub2p/Bfa1p via phosphorylation of Bfa1p by the Polo kinase Cdc5p. Interestingly, activation of spindle checkpoints inhibits Bfa1p phosphorylation, suggesting that these signaling pathways prevent mitotic exit by maintaining the GAP activity of Bub2p/Bfa1p.     

Persistence of naturally acquired cell-mediated immunity to rubella virus during the first trimester of pregnancy

We studied the persistence of naturally acquired cell-mediated immunity to rubella during early pregnancy. We compared lymphocyte transformation responses to phytohemagglutinin and rubella virus in 35 naturally immune women aged 17-37 years, in the first trimester of pregnancy, with 49 naturally immune age-matched nonpregnant controls. A significant lower lymphocyte transformation response to phytohemagglutinin was observed during the first trimester of pregnancy (P = 0.008), but lymphocyte transformation responses to rubella virus were not significantly different (P = 0.901). These data indicate that, in naturally immune women, cell-mediated immunity to rubella virus is not significantly altered by the physiological changes in early pregnancy.     

Effect of antiviral antibody on maintenance of long-term rubella virus persistent infection in Vero cells.

A Vero cell line with a long-term rubella virus persistent infection was maintained for 45 weeks in the presence of anti-rubella virus antibody of sufficient titer to completely neutralize the virus in the culture fluid to determine the effect of the presence of antibody on the maintenance of the persistent infection. Prior to antibody treatment, virus was continuously detected as plaque-forming units in the persistently infected culture fluid. Virus clones that were plaque purified from the persistently infected culture fluid were temperature sensitive and exhibited a reduced efficiency of replication and ability to induce cytopathic effects in Vero cells at the persistently infected culture temperature compared with the standard virus used to initiate the persistently infected culture. Defective interfering RNAs were the major intracellular virus-specific RNA species present in the persistently infected cells. Treatment with antibody failed to cure the persistently infected culture of virus, and the cells retained the ability to release virus after antibody treatment was discontinued. Interestingly, the presence of antibody led to the selection of a population of virus which was markedly less cytopathic for Vero cells than the virus population which was selected during persistent infection in the absence of antibody.     

Effect of rubella vaccination programme in schools on rubella immunity in a general practice population.

Between November 1979 and January 1980 all patients aged 13-21 years who attended a general practice in Glasgow were tested for their immunity against rubella (single radial haemolysis test). All of the women in the sample should have been vaccinated at 13 as part of the rubella vaccination programme, which began in Glasgow in 1971. The programme excludes boys. Of the 77 females and 64 male patients studied, nine (11.7%) and 10 (15.6%), respectively, were susceptible to the infection. For only 34 women was evidence of vaccination documented in the practice records, and three of those either had failed to seroconvert or had antibody below detectable values. Overall there was no significant differences between the proportion of men and women who were susceptible to the disease. The rubella vaccination programme had clearly failed to reduce the number of susceptible women in this practice. Hence the immune state of all girls should be checked at about 15 years of age, so that as many as possible may be rendered immune before they leave school.     

General practitioner fundholding: experience in Grampian.

Proposals for fundholding were greeted with scepticism by many general practitioners, and in Scotland the BMA persuaded the government to allow a scheme to test the arrangements as a demonstration project operating "shadow" practice funds. This allowed the six selected practices to set up administrative and computer systems without the worry of dealing with real money. The shadow fundholding scheme has since been extended to small practices and to a trial of fundholding for all services except accident and emergency. The six practices in the original pilot have all become fundholders and are beginning to effect improvements in the service to their patients. However, with more practices becoming fundholders negotiating contracts with providers is becoming increasingly complicated and more time and money needs to be put into this aspect.     

Passive transfer of local immunity to influenza virus infection by IgA antibody

Secretory IgA is presumed to be the mediator of mucosal immunity based on many studies that show a correlation between protection and secretory IgA titers; however, a causal relationship has not yet been established. Classically, passive transfer of antibody has been used to demonstrate causality, but the passive transfer of local immunity with physiologically transported IgA has not been previously reported. In this study mice were injected intravenously with polymeric IgA (pIgA), monomeric IgA (mIgA), or IgG1 mAb specific for the H1 hemaglutinin of PR8 influenza virus. pIgA was shown to be specifically transported into nasal secretions relative to the mIg. The transported pIgA was functional, as evidenced by its ability to bind to virus in an ELISA assay and to protect nonimmune mice against intranasal infection with H1N1 but not H3N2 influenza virus. Intravenous injection of similar virus-neutralizing doses of anti-influenza IgG1 mAb did not protect against nasal viral challenge. IgA-mediated protection could be abrogated by the intranasal administration of antiserum against the alpha chain of IgA. These data demonstrate the passive transfer of local immunity by the i.v. administration of pIgA antibody and show that the IgA in secretions can protect against influenza virus infection. This general approach could provide a model for the evaluation of the role of local IgA in host defense against other pathogens.