The antimeasles immunity in infants in the 1st year of life

The serological survey of 138 infants aged 8 months and 138 mothers having had protective titers of specific antibodies to measles during pregnancy was made. The study revealed that passively transferred antibodies to measles circulated in infants for a longer time and were detected more frequently under the conditions of breast feeding by mothers having had measles (up to 93.7% of infants). In artificially fed infants, born of mothers having had no measles, but previously vaccinated against this infection, antibodies to measles were detected in rather rare cases (only in 7.3%). In infants, artificially fed, but born of mothers having had measles, the level of antibodies to measles was practically unchanged (81.6%).     

The duration and strength of postvaccinal measles immunity

A prolonged immunoepidemiological follow-up of a large group of children immunized against measles revealed a high epidemiological efficacy of a single vaccination. Cases of measles were registered only among those vaccinees in whose blood sera no specific hemagglutinins were detectable by titration with 4 hemagglutinating units of measles antigen prior to the disease. The study showed that groups of children seronegative with respect to measles appeared, as a rule, after unsatisfactory immunization and not due to loss of postvaccinal immunity with time. Properly immunized children in whom the formation of antimeasles antibodies had occurred in response to the injection of live measles vaccine retained postvaccinal immunity for more that 15 years (the term of observation).     

Reactogenic properties and immunogenicity of measles and mumps vaccines when used by different procedures

In the controlled epidemiological trial the reactogenic and immunogenic properties of live measles vaccine (LMV) and live parotitis vaccine (LPV) were evaluated in identical groups of children immunized in accordance with different schedules: only LMV or LPV, the injection of these preparations mixed in one syringe or with the use of separate syringes, or at an interval of 3 months. The highest number of febrile reactions, rash and catarrhal symptoms was registered among children immunized with LMV, and the lowest number of such reactions in the groups of children immunized with LPV. The injection of LMV and LPV with one syringe or simultaneously with separate syringes decreased the intensity of immune response to the injection of the antigens. Immunization against measles and parotitis by the injection of monopreparations at an interval of 3 months is believed to be most expedient.     

Correlation of titers of antibodies to the measles virus by an immunoenzyme method and in the hemagglutination inhibition reaction

The authors analyze the results of comparative studies on 15 paired sera from children with suspected measles, of 32 sera from children and adolescents aged 1.5 to 16 immunized against measles, and of 21 sera from adults aged 19 to 86 with a history of the disease. EIA proved to be more sensitive than HAIT: the detection rate of positive sera was higher, as were the titers of antibodies detected by it, in examinations of the sera from vaccinated children and the adults. Analysis of the distribution of sera with different titers of antibody to measles virus in EIA and HAIT has revealed a correlation between the titers in the sera with high antibody levels. In the cases with low antihemagglutinin titers, no correlation between the titers determined in the two tests has been observed.     

Measles antibodies in exocrine secretions

The results of the analysis of saliva samples taken from 157 persons aged 1-48 years for the presence of antimeasles antibodies in the neutralization test, the hemagglutination inhibition test and the passive hemagglutination test are presented. The data obtained in this study suggest that antimeasles antibodies can be detected in saliva for many years after the formation of immunity, but quickly disintegrate after a saliva sample is taken.     

Antibodies to Streptococcus pneumoniae antigens in newborn infants

The levels of antibodies to capsular polysaccharide antigens of pneumococci (serotypes 1, 3, 6B, 8, 9N, 15F, 23F), C-polysaccharide and protein antigen of pneumococci in the blood sera of 38 newborn infants at the moment of their birth (umbilical blood) and on the 5th or 6th day of their life, in their mothers' blood sera, as well as in the colostrum and milk of 48 nursing women, have been studied by means of the enzyme immunoassay. The study showed that in the normal course of pregnancy antibodies to pneumococci were transferred transplacentally from the mother to the fetus. Though in most cases their content in the blood of newborn infants was lower than that in maternal blood, it exceeded the average level of antipneumococcal antibodies in children aged 3-12 months. In the milk of nursing mothers considerable amount of IgA antibodies to pneumococci was detected, which might be an additional protective factor with respect to pneumococcal infection in infants.     

Immunostructure of school-age children inoculated against measles

The mass serological survey of school children immunized against measles was carried out by means of the hemagglutination inhibition test. As a result, 20.4% of these school children were found to be seronegative, and in 9.5% of them even the minimum concentration of measles antihemagglutinins (when titrated with 1 hemagglutinating unit of the antigen) was not detected. The accumulation of a considerable seronegative (measles-susceptible) stratum among children of school age occurred due to the low immunogenic potency of some batches of live measles vaccine, used for immunization in 1973, as well as due to the formerly practiced immunization of children under 1 year of age. A direct and close dependence of focal measles morbidity among immunized children having had contacts with the source of infection on the number of children among them, found to be seronegative after titration with 1 hemagglutination unit of measles antigen, was established.     

Rapid serological screening of human sera for the presence of measles virus antibodies in solid-phase immunoenzyme analysis

A single dilution technique has been used for the determination of antimeasles antibody titer. The method involved the plotting of the calibration curve and the characterization of the serum by arbitrary "evaluation units" in comparison with the specially selected positive serum whose titer was taken to be equal to 100 "evaluation units". By means of this method 57 sera obtained from children immunized against measles and 118 sera from non-vaccinated adults aged 18-22 years were examined. The values of the calculated titers were similar to those determined experimentally. This recommends this method for seroepidemiological investigations aimed at determining the level of herd immunity to measles.     

Presence of maternal anti-HBs antibodies does not influence hepatitis B vaccine response in Brazilian neonates

Recently, it was suggested that maternal hepatitis B surface antigen antibodies (anti-HBs) acquired transplacentally could play a negative role in newborn infants' immune response to the hepatitis B vaccine. We compared the hepatitis B virus (HBV) vaccine response in infants born to mothers previously vaccinated against HBV (n = 91) to infants born to mothers who were not previously vaccinated (n = 221). All newborn infants received three intramuscular doses (10 μg) of HBV vaccine (Butang?) at 0,1 and six months. The first dose was administered at the maternity hospital within 12 h of birth. The geometric mean titres of anti-HBs were not different among newborn infants born to mothers who were anti-HBs-negative (492.7 mIU/mL) and anti-HBs-positive (578.7 mIU/mL) (p = 0.38). Eight infants did not respond to the HBV vaccine. Of them, six were born to anti-HBs-negative mothers and two were born to mothers with anti-HBs titres less than 50 mlU/mL. Despite the mother's anti-HBs-positive status, our data show a good immunogenicity of the Brazilian HBV recombinant vaccine in neonates.     

Seroprevalence of measles-, mumps- and rubella-specific IgG antibodies in german children and adolescents and predictors for seronegativity

We have undertaken a seroprevalence study with more than 13,000 children, who had been included in the German KIGGS survey, a representative sample of children and adolescents 0-17 years of age. The IgG titres against measles, mumps and rubella were determined in 1 to 17 year olds While 88.8% of the children were MMR-vaccinated at least once, 76.8% of children aged 1 to 17 years showed prevalence of antibodies to MMR. The highest seronegativity was seen with respect to mumps. Gender differences were most pronounced with regard to rubella IgG titres: girls aged 14 to 17 years were best protected, although seronegativity in 6.8% of this vulnerable group still shows the need of improvement. Search for predictors of missing seroprevalence identified young age to be the most important predictor. Children living in the former West and children born outside of Germany had a higher risk of lacking protection against measles and rubella, while children with a migration background but born in Germany were less often seronegative to measles antibodies than their German contemporaries. An association of seronegativity and early vaccination was seen for measles but not for mumps and rubella. A high maternal educational level was associated with seronegativity to measles and rubella. In vaccinated children, seronegativity was highest for mumps and lowest for rubella. For mumps, high differences were observed for seronegativity after one-dose and two-dose vaccination, respectively. Seronegativity increases as time since last vaccination passes thus indicating significant waning effects for all three components of MMR.     

Concentration and avidity of anti-tetanus antibodies in mother-infant pairs: Relation to immunization time

Abstract The concentration and avidity of anti-tetanus antibodies in two groups of mother-infant pairs were compared. Mothers immunized during pregnancy and their newbons (group A) had significantly higher antibody concentrations than mothers immunized at least a year before their last pregnancy and their newborns (group B) as measured by an indirect enzyme immunoassay (EIA) procedure. Antibody avidity of samples was measured by an inhibition EIA technique and urea denaturation test. Although antibody avidity was higher in group B, the differences were not significant. These findings may represent a secondary antibody response to a protein antigen, when considering that all mothers in both groups had received a primary tetanus vaccination during childhood. In mothers with a history of primary tetanus immunization, a single booster dose of tetanus toxoid during pregnancy is enough to induce protective levels of antibodies with reasonably high avidity in both mother and newborn.     

A calendar of prophylactic inoculations in wide practical use

The validity of immunizations, made in due time in children aged up to 7 years in accordance with the approved immunization schedule, is analyzed in this work. The content of antibodies to diphtheria, tetanus and poliomyelitis antigens in children immunized in accordance with the old and new schedules has been studied. This study has revealed that the injection of adsorbed DPT vaccine to children aged 3-4 months induces fully valid immune response to all antigens under study. The level of measles and parotitis antibodies after the injections of measles and parotitis vaccines, introduced separately and simultaneously, has been measured. The simultaneous administration of these preparations did not decrease the levels of immunity to parotitis and measles.     

IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants

Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.     

Study of combined vaccination against yellow fever and measles in infants from six to nine months

A study has been carried out in the Ivory Coast to assess the efficacy of a combined vaccine against yellow fever and measles relative to that of each vaccine administered separately. Healthy children aged six to nine months were recruited and divided into two age groups: less than seven months (group I) and more than eight months (group II). In each group, they were randomly assigned to receive either yellow fever vaccine only (A), measles vaccine only (B), or the combined vaccine (C). The serological responses to measles and yellow fever were assessed in 219 initially seronegative children 45 days after immunization. More than 90% of the children developed yellow fever haemagglutination inhibiting antibodies. Neither age nor combination with measles vaccine influenced the responses to yellow fever vaccine. Measles haemagglutinational inhibiting antibodies were found in 97% of the children and the seroconversion rate was influenced neither by age nor by combination with yellow fever vaccine. Younger infants had lower titres of measles antibody. No particular adverse reactions were notified during the follow up. This study shows that combined yellow fever and measles vaccines are immunogenic in infants from the age of six months. Controlling yellow fever in endemic areas and the prevention of measles in young infants may greatly benefit by this combination.     

Diaplacental passage of Sarcocystis antibodies in man and rats (author's transl)]

Sera of babies up to the age of 3 months were tested for Sarcocystis antibodies using the indirect immunofluorescence test (IIFT). In addition titre of the Sarcocystis antibody level of litters born to serologic Sarcocystis positive mother rats was compared to those of their mothers. The results are as follows: 1. 45 (= 14.6%) out of 308 sera from babies up to the age of 3 months reacted positively in the Sarcocystis antibody test. 2. 28 (= 62.2%) out of the 45 positive sera were from babies up to 2 weeks old, 13 (= 28.9%) were from babies older than 2 weeks but not more than 4 weeks old, and 2 (=4.4%) each were from babies whose ages ranged from 4 to 8, and 8 to 12 weeks respectively. 3. These babies acquired their Sarcocystis antibodies which decreased in the first 3 months of life from their mothers. 4. Litters born to serologic Sarcocystis positive mother rats also demonstrated Sarcocystis antibodies. The titres of these antibodies were at the same level as their mothers' at birth but reduced gradually so that most of these young rats were negative at the age of 3 months. 5. Suckling rats born to Sarcocystis negative mothers but positive fathers remained negative. 6. Serologic positive mother and father rats still demonstrated Sarcocystis antibodies in the sera at a time when their litters have become negative. 7. Sarcocystis antibodies could be passed onto the newborn from their positive mothers in both man and rats. 8. These antibodies were probably passed onto the newborn through the placenta but their passage through the colostrum and the mother's milk cannot be ruled out.     

Passive smoking in utero: its effects on neonatal appearance.

Smoking causes changes in the appearance of adults and has profound effects on the fetus, but little is known about its effects on the appearance of newborn infants. Two colour photographs (face and whole body) of 15 newborn infants (seven born to mothers who had smoked during pregnancy and eight born to mothers who had not) were shown to 100 medical and nursing staff, who in a double blind trial were asked to identify which babies had been born to smokers. The mean number correctly identified was 9.1, which was significant compared with the number expected by random selection (7.5). No specific features were identified that distinguished the two groups of infants; selection was intuitive. Nevertheless, the fact that differences can be detected in some way may be useful for antismoking health education.     

妊娠期糖尿病妇女体重指数对新生儿体脂的影响

本研究旨在通过评估新生儿的精确磁共振成像,确定妊娠期糖尿病(GDM)、肥胖母亲的后代与正常体重女性的后代相比,新生儿脂肪沉积模式是否存在早期影响。对正常体重母亲(n=13)和肥胖母亲(GDM)(n=12)的25名新生儿进行磁共振成像测量皮下和腹部脂肪和磁共振波谱,以测量1~3岁时肝内脂质(IHCL)脂肪的含量。结果表明,与正常体重母亲所生的婴儿相比,肥胖/妊娠糖尿病母亲所生婴儿的IHCL平均增加了68%。对于所有婴儿,IHCL与孕妇体重指数相关,但与皮下脂肪无关。新生儿肝脏沉积物与母亲体重指数高度相关。这一发现可能有助于了解儿童非酒精性脂肪肝的发病起源。     

Protective efficacy against group B streptococcal infection in neonatal mice delivered from preimmunized pregnants

Neonatal mice delivered from mothers preimmunized with heated or formalinized whole cell vaccines of type Ia, Ia/c and III/c group B streptococci were infected with each type of bacteria, and then serum antibodies of mothers and neonates who survived the experiments were measured by enzyme-linked immunosorbent assay. The relationship between the protectivity in neonate mice and the antibody titers to the type specific polysaccharide antigens and the protein c antigen of their sera were examined. In the Ia-immunized group which showed high protection against the type Ia infection, anti-Ia IgG antibody titers were low, and anti-protein c IgG antibody was not detected. Type Ia/c and III/c vaccines were highly effective against both type Ia/c and III/c infection, but less effective in type Ia infection. The protein c antigen was identified in both type strains by the double diffusion assay, and the IgG antibodies to the protein c were significantly high in sera of both maternal mice immunized with types Ia/c or III/c organisms and their newborn infants. High titers of the protein c IgG antibody retained 3 to 4 weeks after the last injection of vaccines which corresponded to the period of pregnancy and lactation. Small amounts of IgM antibody to all antigens were detected only in maternal sera. These results suggest that IgG antibodies to the protein c antigen and to the type-specific polysaccharide antigens are equally important protective factors which are transferable from preimmunized mothers to their newborn infants through placenta and/or lactation.     

HIV-infected children living in Central Africa have low persistence of antibodies to vaccines used in the Expanded Program on Immunization

Background

The Expanded Program on Immunization (EPI) is the most cost-effective measures to control vaccine-preventable diseases. Currently, the EPI schedule is similar for HIV-infected children; the introduction of antiretroviral therapy (ART) should considerably prolong their life expectancy.

Methods and Principal Findings

To evaluate the persistence of antibodies to the EPI vaccines in HIV-infected and HIV-exposed uninfected children who previously received these vaccines in routine clinical practice, we conducted a cross-sectional study of children, aged 18 to 36 months, born to HIV-infected mothers and living in Central Africa. We tested blood samples for antibodies to the combined diphtheria, tetanus, and whole-cell pertussis (DTwP), the measles and the oral polio (OPV) vaccines. We enrolled 51 HIV-infected children of whom 33 were receiving ART, and 78 HIV-uninfected children born to HIV-infected women. A lower proportion of HIV-infected children than uninfected children had antibodies to the tested antigens with the exception of the OPV types 1 and 2. This difference was substantial for the measles vaccine (20% of the HIV-infected children and 56% of the HIV-exposed uninfected children, p<0.0001). We observed a high risk of low antibody levels for all EPI vaccines, except OPV types 1 and 2, in HIV-infected children with severe immunodeficiency (CD4⁺ T cells <25%).

Conclusions and Significance

Children were examined at a time when their antibody concentrations to EPI vaccines would have still not undergone significant decay. However, we showed that the antibody concentrations were lowered in HIV-infected children. Moreover, antibody concentration after a single dose of the measles vaccine was substantially lower than expected, particularly low in HIV-infected children with low CD4⁺ T cell counts. This study supports the need for a second dose of the measles vaccine and for a booster dose of the DTwP and OPV vaccines to maintain the antibody concentrations in HIV-infected and HIV-exposed uninfected children.     

Protection against lethal measles virus infection in mice by immune-stimulating complexes containing the hemagglutinin or fusion protein.

The importance of each of the two surface glycoproteins of measles virus in active and passive immunization was examined in mice. Infected-cell lysates were depleted of either the hemagglutinin (H) or fusion (F) glycoprotein by using multiple cycles of immunoaffinity chromatography. The products were used to prepare immune-stimulating complexes (iscoms) containing either F or H glycoprotein. Such complexes are highly immunogenic, possibly as a result of effective presentation of viral proteins to the immune system [B. Morein, B. Sundquist, S. H?glund, K. Dalsgaard, and A. Osterhaus, Nature (London) 308:457-460, 1984]. Groups of 3-week-old BALB/c mice were inoculated with the iscom preparations. All animals developed hemolysis-inhibiting antibodies, whereas only sera of animals immunized with the iscoms containing the H glycoprotein had hemagglutination-inhibiting antibodies. Sera from animals immunized with the H or F preparation only precipitated the homologous glycoprotein in radioimmune precipitation assays. The immunized animals were challenged with a lethal dose of the hamster neurotropic variant of measles virus. Of the 7-week-old animals in the nonimmunized control group, 50% died within 10 days after challenge. No animals in the immunized groups showed symptoms of disease throughout the observation period of 3 months. Passive administration of anti-H monoclonal antibodies gave full protection against the 100% lethal acute infection with the hamster neurotropic variant of measles virus in newborn mice, whereas anti-F monoclonal antibodies failed to protect the animals. This study emphasizes that both H and F glycoproteins need to be considered in the development of measles virus subunit vaccines.