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1.
Infant guinea-pigs born to mothers immunized against influenza virus by infection during pregnancy were reared from birth by non-immune foster mothers. As a control for the effects of fostering, a similar group were fostered to immune mothers. Fostering, regardless of the immune state of the foster-mother, increased the susceptibility of the infant to upper respiratory tract infection. Increased susceptibility was associated with ablation of the infants IgM and IgA antibody responses and reduced secretion of transplacentally acquired IgG antibody in nasal secretions. In the reciprocal experiment, infants of non-immune mothers fostered to immune mothers cleared virus more rapidly than their peers who were fed by their own mothers. This protective effect was associated with an enhanced nasal IgM and IgA antibody response. Infants of immune mothers separated from their mothers at birth and hand-reared on a cow's-milk-based formula feed suffered an increased susceptibility to the virus similar to that seen in fostered infants. Addition of a pool of expressed milk from a group of immune mothers, including their own, to the feed of hand-reared infants did not reduce their susceptibility. However, a further group of infants fed a non-cellular whey fraction of the same milk pool secreted significantly lower titres of virus. This increased protection was associated with elevated levels of IgG antibody secretion into nasal washes early in infection.  相似文献   

2.
Infant guinea-pigs born to mothers immunized against influenza virus by infection during pregnancy were reared from birth by non-immune foster mothers. As a control for the effects of fostering, a similar group were fostered to immune mothers. Fostering, regardless of the immune state of the foster-mother, increased the susceptibility of the infant to upper respiratory tract infection. Increased susceptibility was associated with ablation of the infants IgM and IgA antibody responses and reduced secretion of transplacentally acquired IgG antibody in nasal secretions. In the reciprocal experiment, infants of non-immune mothers fostered to immune mothers cleared virus more rapidly than their peers who were fed by their own mothers. This protective effect was associated with an enhanced nasal IgM and IgA antibody response. Infants of immune mothers separated from their mothers at birth and hand-reared on a cow''s-milk-based formula feed suffered an increased susceptibility to the virus similar to that seen in fostered infants. Addition of a pool of expressed milk from a group of immune mothers, including their own, to the feed of hand-reared infants did not reduce their susceptibility. However, a further group of infants fed a non-cellular whey fraction of the same milk pool secreted significantly lower titres of virus. This increased protection was associated with elevated levels of IgG antibody secretion into nasal washes early in infection.  相似文献   

3.
Two alternative hypotheses have been generated to account for seasonal variation in the birth weight of human infants born in industrialized countries. First, it has been hypothesized that low ambient temperature during the second trimester of gestation decreases birth weight. Second, it has been hypothesized that exposure to bright sunshine during the first trimester increases birth weight. We tested these two hypotheses to determine which, if either, accounted for seasonal variation in birth weight of full-term infants. Birth weight data, collected over a 5-year period, were analyzed as a function of peak and trough sunshine and ambient temperature. Although there was no effect of ambient temperature during any trimester on birth weight, infants whose mothers were exposed to peak sunshine during their first trimester were born significantly heavier than infants whose mothers experienced trough levels of sunshine during the same trimester. Furthermore, infants whose mothers were exposed to trough levels of sunshine during their second and third trimesters were born significantly heavier than infants whose mothers were exposed to peak levels of sunshine during the same trimesters. We hypothesize that high levels of sunshine during early gestation may increase the level of insulin-like growth factor (IGF)-1, facilitating prenatal growth.  相似文献   

4.
To determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placental transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIV-infected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (>1.0 μg/ml) at birth in 90% of HEU infants and all U.S. infants. HEU infants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P = 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.  相似文献   

5.
We have recorded the systemic and mammary/mucosal immune responses of women following natural infection with RS virus during the second and third trimesters of pregnancy. Anti-RS virus IgG antibody levels in the sera of women collected in the first trimester of pregnancy showed a bimodal distribution with high and low antibody groups. Antibody levels increased after exposure to the winter RS virus epidemic in the second trimester of pregnancy, probably as a result of infection but only for women in the low antibody group. Despite the increases, antibody levels for these women remained well below those of the high antibody group. There was no rise in mean antibody levels after exposure in the third trimester, even among women with low antibody, suggesting a degree of immunosuppression in late pregnancy. There was no evidence that infection during pregnancy was associated with adverse consequences for the infant. Exposure to RS virus in the first two trimesters, but not the third, was associated with high colostral IgA antibody levels that were maintained in the milk throughout the first 7 weeks of lactation. There was a significant correlation between colostral and maternal nasal IgA antibody levels at delivery. Levels of blood or colostral lymphocyte transformation responses at delivery were unaffected by exposure to RS virus in pregnancy. These observations upon natural infection suggest that vaccination during pregnancy is likely to achieve only marginal effects upon serum antibody levels but boost maternal mammary/mucosal immunity.  相似文献   

6.
A comparison of inactivated intramuscular and live intranasal influenza A vaccines in young children undergoing primary immunization might be expected to show differences in serum and local mucosal antibody responses. To demonstrate such differences, serum and local respiratory tract antibody responses of young children vaccinated with intranasal live, attenuated, cold-adapted (H3N2 or H1N1), or intramuscular inactivated (H3N2) influenza A vaccines were examined for one year after vaccination. Antibody responses were measured by hemagglutination-inhibition (HAI) and class-specific enzyme-linked immunosorbent assay (ELISA). One year after vaccination, live intranasal vaccinees had significantly less decay of serum HAI (p = 0.025) and IgG antibody (p = 0.01) directed against the influenza hemagglutinin and neuraminidase than did intramuscular inactivated vaccinees. Nasal secretory IgA developed almost exclusively in live vaccinees and persisted for up to one year. Persistent nasal secretory IgG was detected in both live and inactivated vaccinees. Live vaccination not only stimulates a more durable serum antibody response, but also induces long-lasting local respiratory tract IgA antibody that may play an important role in host protection.  相似文献   

7.
BACKGROUND: The immune status and allergen exposure of the mother may influence the immune response in the offspring after birth. This relationship may be important both for allergen avoidance strategies and, alternatively, for allergy prophylaxis by allergen exposure of the mother. OBJECTIVE: The aim of the present study was to investigate the effect of allergen immunization of the mother during pregnancy and postpartum, in relation to the allergy-related immune response (IgE) and the non-allergy-related (IgG2a) response in the offspring. METHODS: Pregnant NIH/OlaHsd females were immunized three times during pregnancy and one time postpartum with ovalbumin and the adjuvant Al(OH)3, and the offspring's ovalbumin-specific IgE, IgG1 and IgG2a responses were measured after challenge with the same allergen as young adults. Ovalbumin-specific IgE, IgG1 and IgG2a responses were also analysed in offspring of NIH/OlaHsd females immunized once at different times during pregnancy: about 3 days into pregnancy, mid-pregnancy (10 days into pregnancy) and about 4 days before giving birth (17 days into pregnancy). RESULTS: Allergen immunization of mother during pregnancy and postpartum significantly reduced the IgE response in the progenies, whereas the IgG2a response to the same allergen was increased. Allergen immunization of the mother 3 days into pregnancy resulted in a significantly lower IgE response in offspring compared with the response in offspring of non-immunized mothers and in offspring of mothers immunized 17 days into pregnancy. CONCLUSIONS: Maternal allergen immunization might favour selection for an allergen-specific Th1-dependent antibody response in the offspring. Our results indicate that IgE suppression is stronger after maternal allergen exposure during early pregnancy than after exposure in late pregnancy.  相似文献   

8.
BACKGROUND. Intrauterine transmission of cytomegalovirus (CMV) can occur whether a mother has prior immunity or acquires CMV for the first time during pregnancy. The degree of protection afforded an infected infant by the presence of antibody in the mother before conception is uncertain. METHODS. We compared the outcomes of CMV-infected infants born to mothers who acquired primary CMV infection during pregnancy (primary-infection group) with those of CMV-infected infants born to mothers with immunity (recurrent-infection group). Screening for viruria identified 197 newborns with congenital CMV infection. Stored serum samples were used to categorize maternal infection as either primary or recurrent. We followed 125 infants from the primary-infection group and 64 from the recurrent-infection group. Serial medical, audiologic, psychometric, and eye examinations were used to identify sequelae of CMV infection. RESULTS. Only infants in the primary-infection group had symptomatic CMV infection at birth (18 percent). After a mean follow-up of 4.7 years, one or more sequelae were seen in 25 percent of the primary-infection group and in 8 percent of the recurrent-infection group. Thirteen percent of infants whose mothers had primary infection during pregnancy had mental impairment (IQ less than or equal to 70), as compared with none of those whose mothers had recurrent CMV infections. Sensorineural hearing loss was found in 15 percent of those in the primary-infection group and in only 5 percent of those in the recurrent-infection group. Bilateral hearing loss was identified only among children in the primary-infection group (8 percent). CONCLUSIONS. The presence of maternal antibody to CMV before conception provides substantial protection against damaging congenital CMV infection in the newborn. Primary maternal infection during pregnancy is associated with more severe sequelae of congenital CMV infection.  相似文献   

9.
Since 1976, sera obtained serially from 10,218 pregnant women during the first, second, and third trimesters of gestation and cord sera were tested for CMV complement-fixing (CF) and immunofluorescent (IF) antibodies. CMV IgG-IF antibody was positive in 9,735/10,218 (95%) in the first trimester, and a significant rise of CF antibodies during pregnancy was found in 70/9,206 (0.76%) of the seropositive group and in 5/438 (1.14%) of the seronegative group. IgM antibody was found in 6/9,206 (0.06%) of seropositive women during the first trimester and in 7/70 (10.0%) of seropositive mothers with CF antibody rise and in 4/5 of seroconverted mothers of the seronegative group, suggesting that the incidence of primary infection with CMV during pregnancy was approximately 1% of susceptible women. All the mothers with immune response had infants with neither viruria nor IgM antibody in the cord blood, whereas seropositive mothers without an immune response had infants with viruria (7/1,826; 0.4%) or with IgM antibody in the cord blood (6/9,136; 0.06%). None of these 13 babies, shedding CMV or with IgM IF antibody, had physical or mental retardation. CMV IgG-IF antibody was present in almost 80% of infants between 7 and 12 months of age in 1988, suggesting that perinatal or postnatal CMV infection may occur in infants born to seropositive mothers in 70-80% of pregnancies.  相似文献   

10.
We studied the pattern of type 1 diabetes-associated autoantibodies during pregnancy and the transplacental transfer of these autoantibodies to the fetal circulation and searched for possible signs of prenatal induction of beta-cell autoimmunity in newborn infants. The population comprised 208 mothers and their newborn infants. Seventy-four of the mothers (36%) had type 1 diabetes and 134 (64%) of the infants had an affected father or sibling. Blood samples were obtained from the mother at the end of the first trimester and at delivery, and from the cord blood of the newborn infant. Close to 40% of the mothers with type 1 diabetes had antibodies to islet cells (ICA), 55% to glutamic acid decarboxylase (GADA) and 54% to the IA-2 protein (IA-2A) in early pregnancy, whereas the corresponding frequencies in the nonaffected mothers were 5.2%, 5.2% and 3.0%. No significant changes could be seen in autoantibody levels during pregnancy, and there was a close correlation between the two maternal samples. One third of the infants of mothers with type 1 diabetes tested positive for ICA, 50% for GADA and 51% for IA-2A. Six percent of the infants of nondiabetic mothers had ICA, 2.2% GADA and none had IA-2A. None of the infants of the antibody negative mothers had antibodies in their cord blood. These observations indicate that the immunomodulatory effect of pregnancy on signs of beta-cell autoimmunity is weak, but if diabetes-associated autoantibodies are present in the mother, most of them are transferred to the fetal circulation. Our data do not provide any support for fetal induction of beta-cell autoimmunity.  相似文献   

11.
While vaccines are effective in adults, they are less successful in newborns and infants. Neonatal unresponsiveness to vaccines could be owing to immaturity of lymphocytes and/or to inhibition by maternal antibodies. Unresponsiveness of newborn to vaccines can be overcame by genetic immunization. In the present study we investigated the effect of maternal antibodies on the anti-influenza virus protective response in progeny born to dams immunized with plasmid containing the hemagglutinin gene or UV-inactivated virus. The effect of maternal antibodies was studied in plasmid immunized F1 mice born to BALB/c dams, previously immunized with virus or plasmid and crossed with C57BL/6 males, as well as in offspring born to BALB/c dams immunized with plasmid and then immunized with UV-inactivated WSN virus. We have found that the inhibition period of the anti-HA antibody response in offspring born to dams immunized with DNA is shorter than that of offspring born to dams immunized with virus. Furthermore, there is a persistent inhibitory effect on B cells from offspring born to dams immunized with virus or injected with antiviral monoclonal antibodies (MoAb), after the decline of maternal antibody titers. The analysis of the haemagglutinin-specific clonotype reactivity pattern of offspring born to dams immunized with inactivated influenza virus or with a plasmid showed that clonotypes producing antibodies specific for the immunizing virus strain were predominant in offspring born to dams immunized with DNA compared to those born to dams immunized with virus. Maternal antibodies do not affect cell-mediated immunity. These findings might be used to design efficient vaccination schedules for newborns and infants.  相似文献   

12.
To eradicate measles in developing nations a vaccine capable of being administered at birth may be necessary. We immunized newborn rhesus macaques with naked DNA encoding the measles virus hemagglutinin, fusion and nucleoprotein genes. Prior to vaccination we passively transferred measles immunoglobulin to mimic maternal antibody. In the presence or absence of measles immunoglobulin, 23 of 25 infant macaques had detectable cell mediated immunity and 16 had protective levels of neutralizing antibody. The co-administration of an IL-2/IgG plasmid augmented the vaccine, increasing cell mediated immunity in all infants and increasing the antibody response in infants vaccinated without immunoglobulin. We show for the first time that DNA vaccination can protect a newborn primate from the high-level viremia that correlates with severe measles, even in the presence of maternal antibody. Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine.  相似文献   

13.
To determine the effects of changes in maternal cigarette use during pregnancy on birthweight, a sample of Caucasian births free of major malformations (n = 9,943) was examined. Births were stratified by level of maternal smoking in the first trimester and subdivided according to whether the mother continued at the same level, reduced, or quit by the second trimester. Birthweights were adjusted statistically for extraneous variables. As expected, second and third trimester cigarette use was associated with birthweight, but so too was cigarette use during the first trimester, and the effect of quitting varied significantly with the level of first trimester smoking. Among moderate and light smokers, who comprise the majority of smokers, quitting before the second trimester is associated with heavier infants. However, infants of heavy smokers who quit by the second trimester did not weigh significantly more than infants of mothers who continued to smoke heavily throughout pregnancy, and weighed significantly less than infants of nonsmokers or other smokers who quit. Thus, quitting by the end of the first trimester may not completely negate the effect of heavy first trimester smoking, and the adaptive value of qutting is unequal among different levels of first trimester smoking. Further research on prenatal growth should take cigarette smoking in all trimesters into account. © 1994 Wiley-Liss, Inc.  相似文献   

14.
Allergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen-specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non-specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.  相似文献   

15.
Rhesus monkeys (Macaca mulatta) were immunized with purified P fimbriae from Escherichia coli during the last trimester of pregnancy. Infants born of these mothers were compared with those from nonimmunized rhesus mothers. A delay in the onset of renal disease after bladder infection showed protection from passive immunization. This was associated with a high antibody titer in serum. In addition to delayed onset of renal infection, a decreased number of immunized monkeys developed pyelonephritis.  相似文献   

16.
Respiratory syncytial virus (RSV) causes significant infant mortality worldwide and a vaccine may be available soon. This study determined age-stratified anti-RSV antibody positivity (enzyme-linked immunosorbent assay [ELISA]) at Pune, India (cord blood-85 years). Antibody positivity declined from 100% at birth to 71.3% (3 months), and 0.7% (6 months). A significant rise was noted at 15 months (16%), 16 to 24 months (64.5%) and 4 years (95.2%) with concomitant IgM-anti-RSV positivity indicative of recent infection. Antibody decline was higher in infants born preterm than full-term. Across subsequent age groups including the elderly, antibody positivity was similar and comparable, suggestive of repeated exposure to the virus. Early protection/vaccination is essential for the infant population.  相似文献   

17.
The objective of the investigation was to assess whether children of mothers who acquired measles antibodies resp. immunity by vaccination are at least for the first six months of their life protected by maternal antibodies. A group of fifty pregnant women mean age 18 years incl. their umbilical blood and blood of their children, mostly 5-6 months after birth, were examined by the haemagglutination inhibition and immunoenzymatic test. The levels of measles antibodies were detected in 11 women immunized against measles in cca 1970 and in 26 revaccinated women mostly after 5 to 11 years. In once vaccinated mothers and their umbilical bloods the mean HI titres were 1:8.5 and 1:14 resp. and the mean EIA titres were 1:3600 and 1:3040 resp. As to the eight newborn children at the age of 5 and 6 months 6 children did not have any protective antibodies. In twice vaccinated women and their umbilical bloods the mean HI titre was 1:10 and 1:16.4 resp. and EIA titres were 1:2937 and 1:3784 resp. Of the 15 newborn infants at the age of 4 to 6 months 11 infants did not have any protective antibodies. In 8 mothers without vaccination records and their umbilical bloods the mean HI titre was 1:7.5 and 1:25.5 and mean EIA titres were 1:8229 and 1:7360 resp. In none of their children at the age of 6 months measles antibodies were found. The finding of the lack of protection in children older than 6 months stimulates further research of the problem.  相似文献   

18.
We examined immunization with an inactivated, gp120-depleted human immunodeficiency virus (HIV) antigen in incomplete Freund's adjuvant (IFA), also containing a sequence of immunostimulatory (ISS) DNA, during the last trimester of pregnancy and neonatally in a rat model. Pregnant rats were immunized in the third trimester and their litters were immunized during the newborn period. In addition, litters of rats from non-immunized mothers were immunized during the neonatal period. As another control, pregnant rats were immunized and their litters analysed. Supernants from peripheral blood mononuclear cells (PBMCs) were assayed from newborns at 4 weeks of age for HIV-specific interferon-gamma (IFN-gamma), HIV-specific regulated on activation, normal, T-cell expressed, and secreted (RANTES), and serum for p24 antigen-specific immunoglobulin G (IgG) production. In the animals whose pregnant mothers were immunized and were also immunized during the neonatal period, we observed HIV-specific IFN-gamma production and HIV-specific RANTES production, but weak p24 IgG antibody production. Animals immunized only during the neonatal period developed the highest levels of HIV-specific IFN-gamma production, but somewhat lower levels of HIV-specific RANTES and p24 IgG antibody production. The group of animals whose mothers had received immunizations during the last trimester of pregnancy, but were not immunized during the neonatal period, developed the strongest p24 IgG antibody levels, but little or undetectable HIV-specific IFN-gamma or RANTES production. Neonatal immunization resulted primarily in cell-mediated immune responses, while animals born to mothers who were immunized during the last trimester had primarily an antibody-mediated immune response. Immunization of pregnant animals followed by neonatal immunization resulted in a mixed cell-mediated/antibody type profile in the neonatal animal. Future studies should provide insights into neonatal immunity and potential vaccine approaches to prevent neonatal infection and perinatal transmission.  相似文献   

19.
The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.  相似文献   

20.
Eight women who had given birth to infants contracting neonatal septicemia with group B streptococci (GBS) were immunized with a 14-valent pneumococcal vaccine (Pneumovax). Type-specific IgM and IgG antibodies against 6 pneumococcal types were determined before and after vaccination. Ten healthy age-matched women were also vaccinated and served as controls. The study group showed significantly higher preimmune IgM levels against 3 of the 6 pneumococcal antigens, and lower IgG levels against 1 antigen. However, 6 weeks as well as 11/2 years after the immunization, no significant differences in IgG or IgM antibody levels could be demonstrated between the 2 groups. Before vaccination, significantly more study group women showed an arbitrary IgG/IgM ratio below 10 against pneumococcal types 1, 6A, 7F, 14 and 23F. 11/2 years after vaccination, the ratio was significantly lower for antibodies against 2 other types, 6A and 7F. We suggest, as a working hypothesis, that mothers of GBS-infected infants differ in their capacity to switch from IgM to IgG production.  相似文献   

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