Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice

The transfer of maternal antibodies to the offspring and their inhibitory effects on active infant immunization is an important factor hampering the use of certain vaccines, such as measles or respiratory syncytial virus vaccine, in early infancy. The resulting delay in protection by conventional or novel vaccines may have significant public health consequences. To define immunization approaches which may circumvent this phenomenon, experiments were set up to further elucidate its immunological bases. The influence of maternal antibodies on antibody and T cell responses to measles hemagglutinin (MV-HA) were analyzed following MV-HA immunization of pups born to immune or control BALB/c mothers using four different antigen delivery systems: live or inactivated conventional measles vaccine, a live recombinant canarypox vector and a DNA vaccine. High levels (> 5 log10) of maternal anti-HA antibodies totally inhibited antibody responses to each of the vaccine constructs, whereas normal antibody responses were elicited in presence of lower titers of maternal antibodies. However, even high titers of maternal antibodies affected neither the induction of vaccine-specific Th1/Th2 responses, as assessed by proliferation and levels of IFN-gamma and IL-5 production, nor CTL responses in infant mice. On the basis of these unaltered T cell responses, very early priming and boosting (at 1 and 3 weeks of age, respectively) with live measles vaccine allowed to circumvent maternal antibody inhibition of antibody responses in pups of immune mothers. This was confirmed in another immunization model (tetanus toxoid). It suggests that effective vaccine responses may be obtained earlier in presence of maternal antibodies through the use of appropriate immunization strategies using conventional or novel vaccines for early priming.     

Social stress in pregnant squirrel monkeys (Saimiri boliviensis peruviensis) differentially affects placental transfer of maternal antibody to male and female infants.

The capacity of prenatal stress to disrupt the placental transfer of maternal antibody was evaluated in neonatal squirrel monkeys (Saimiri boliviensis peruviensis) gestated under different pregnancy conditions. Normal squirrel monkey offspring (n?=?63) were compared with infants generated from pregnancies that involved either a single or 3 periods of disturbance (ns?=?21 and 29, respectively). At parturition, levels of antibody (IgG) were determined in mothers and neonates. Only the chronic disturbance condition significantly altered antibody levels in the mothers, resulting in lower IgG. Antibody transfer to the fetus was also affected only by chronic disturbance. In this case the effect was bidirectional, influenced by the sex of the infant. Males were born with lower levels, whereas female infants actually had higher-than-normal IgG, despite lower titers in their mothers. Because virtually all IgG is derived from the prenatal transfer of maternal antibody, it indicates that the sex of the fetus differentially affected this placental process. The IgG receptor may have been up-regulated selectively on the placentas of female fetuses, compensating for reduced antibody in the disturbed mothers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antigenic and molecular characterization of wild type 1 poliovirus causing outbreaks of poliomyelitis in Albania and neighboring countries in 1996

Mass vaccination has led poliomyelitis to become a rare disease in a large part of the world, including Western Europe. However, in the past 20 years wild polioviruses imported from countries where polio is endemic have been responsible for outbreaks in otherwise polio-free European countries. We report on the characterization of poliovirus isolates from a large outbreak of poliomyelitis that occurred in Albania in 1996 and that also spread to the neighboring countries of Yugoslavia and Greece. The epidemics involved 145 subjects, mostly young adults, and caused persisting paralysis in 87 individuals and 16 deaths. The agent responsible for the outbreak was isolated from 74 patients and was identified as wild type 1 poliovirus by both immunological and molecular methods. Sequence analysis of the genome demonstrated the involvement of a single virus strain throughout the epidemics, and genotyping analysis showed 95% homology of the strain with a wild type 1 poliovirus strain isolated in Pakistan in 1995. Neutralization assays with both human sera and monoclonal antibodies were performed to analyze the antigenic structure of the epidemic strain, suggesting its peculiar antigenic characteristics. The presented data underline the current risks of outbreaks due to imported wild poliovirus and emphasize the need to improve vaccination efforts and also the need to implement surveillance in countries free of indigenous wild poliovirus.     

Serologic marker as indicator of no circulation of poliovirus in Cuba

The surveillance of the circulation of the wild poliovirus is an essential element for the eradication of poliomyelitis. The Pan-American Health Organization emphasises on the etiological study of acute flaccid paralysis in order to achieve this aim. The characteristics of our program against this entity allowed to use the presence of antibodies in a sample obtained in February from the infant population born on July during the previous year as criteria to know the circulation of wild poliovirus. In 727 infants studies in the country (5% of the total number of births during July), 99.1% showed no antibodies with a titre equal or greater than 1:10. Low titres found in 7 infants were considered as a remnant from maternal transmission. Results obtained represent a strong evidence of the fact that there is no environmental circulation of poliovirus during the period which had the greatest incidence of the disease.     

Caregiving behaviors and early cognitive development as related to ordinal position in preterm infants

Naturalistic home observations of 54 preterm infants and their caregivers were made when the infants were 1, 3 and 8 months of age. Differences were found in the kinds of everyday transactions which occur with preterm infants raised with and without siblings. At 1 month of age the care of firstborn and later-born infants was similar in most ways. At 3 months and 8 months firstborn infants clearly received more responsive care and more stimulation from their mothers than later-born infants. Furthermore, the firstborn infant received more social transactions from anybody. Firstborn preterm infants obtained higher Gesell developmental scores than later-born infants, replicating results reported with infant test performance of full-term infants.     

Infant and Maternal Behaviors Regulate Infant Reactivity to Novelty at 6 Months.

Three issues were investigated: (a) the regulatory effects of presumed infant and maternal regulation behaviors on infant distress to novelty at 6 months, (b) stability of infant regulatory effects across contexts that vary in maternal involvement, and (c) associations and temporal dynamics between infant and maternal regulation behaviors. Participants were 87 low-risk infants and their mothers, observed at 6 months postpartum during infant exposure to novel toys. Contingencies derived from sequential analyses demonstrate that, by 6 months, some infants reduce their own distress to novelty by looking away from the novel toy or self-soothing, maternal engagement and support have comparable effects, and certain infant and maternal behaviors co-occur. Moreover, infants whose mothers engaged contingently when they looked away from the novel toy expressed less distress than comparable infants whose mothers did not. These findings implicate both infants and mothers in the development of emotion regulation during the infant's first year. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of diarrhea on the humoral response to oral polio vaccination

OBJECTIVE: The purpose of this study was to measure the effect of concurrent diarrheal illness on seroconversion to trivalent oral polio vaccine (OPV). METHODS: Six- to 16-week-old infants with acute diarrhea and age-matched controls received single doses of OPV at enrollment, 4 weeks after enrollment and 8 weeks after enrollment. Serum specimens were obtained at enrollment, before the second OPV dose and 4 weeks after the third OPV dose for measurement of antibody titers to polio virus by the microneutralization assay. RESULTS: Four weeks after the first OPV dose, the serologic responses to poliovirus types 2 and 3 in the case cohort were lower by 26 and 34%, respectively, than in the control cohort (P < 0.002 for both comparisons). Poliovirus type 2 and 3 geometric mean antibody titers in the diarrhea cohort were approximately 50% of the geometric mean antibody titers in the control cohort (235 (95% confidence interval (CI) 154 to 359) vs. 446 (95% CI 350 to 569) and 64 (95% CI 45 to 90) vs. 112 (95% CI 88 to 143), respectively, P < 0.01 for both comparisons). After the third OPV dose the seroconvertion rates to poliovirus types 2 and 3 each remained about 10% lower in the case cohort than in the control cohort, but the differences were not statistically significant. CONCLUSION: Concurrent acute diarrhea adversely affects seroconvertion rates of type 2 and 3 polioviruses among infants in Bangladesh receiving the first dose of trivalent OPV.     

In utero exposure to terbutaline: effects on infant behavior and maternal self-esteem

OBJECTIVE: Little is known about correlates of infant behavior after tocolytic intervention. This study investigated three related questions: (a) Are there any behavioral differences in infants exposed in utero to terbutaline and infants not exposed? (b) Is the mother's perception of her infant influenced by group status? (c) Is maternal self-esteem influenced by group status? DESIGN: Group comparison over time of infants exposed in utero to terbutaline and infants not exposed. Group mean cluster scores and recovery curves were compared. Mothers' responses to a series of questionnaires were compared according to group status. The first author remained blind to group status until all measures were completed on all participants. SETTING: Recruitment and first administration of the Brazelton Neonatal Behavioral Assessment Scale occurred in two regional hospitals, at Minneapolis and St. Paul. Subsequent administrations took place in the infants' homes. PARTICIPANTS: Forty-eight healthy, full-term (> or = 37 weeks gestational age) neonates and their mothers, 16 of whom had been given terbutaline, and 32 control subjects. MAIN OUTCOME MEASURES: Brazelton Neonatal Behavioral Assessment Scale was administered three times to each neonate. Mothers completed the Infant Characteristics Questionnaires, the Neonatal Perception Inventories, and the Maternal Self-Report Inventory. RESULTS: Significant differences were found between the two groups of infants on the habituation cluster at Time 1 and the autonomic stability cluster at Time 1 and Time 2. No significant group differences were found in the mothers' responses to the questionnaires. CONCLUSIONS: Nurses can assure parents that neonates exposed to terbutaline, although they may exhibit initial difficulties with behavioral organization, recover well over the course of the neonatal period. In addition, nurses can help mothers discover methods that will help calm their newborns.     

Maternal directiveness and infant compliance at one year of age: a comparison between mothers and their developmentally-delayed infants and mothers and their nondelayed infants

Maternal directiveness and infant compliance at one year of age were observed in social interactions between mothers and their handicapped and nonhandicapped infants. Eleven nondelayed, typically developing infants, and nine developmentally delayed infants, matched for chronological age, were observed in a free play situation with their mothers. Mothers of the delayed infants attempted to direct their children's play significantly more than those with nondelayed infants, and they engaged more frequently in social play involving physical contact with their infants. Nondelayed infants complied with their mothers' directives more than the developmentally delayed infants. Further study of infant capabilities and maternal affect and behaviors with this age group is suggested.     

Links between maternal care and persistent infant crying in the early months

A community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups--of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers--were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below-optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings' implications for professionals are discussed.     

Social network relationships as sources of maternal support and well-being.

Explored the social networks available to mothers of infants, focusing on the contribution of specific relationships to maternal well-being. 43 mothers (aged 21–39 yrs) of 13-mo-old infants were asked to position individuals who were close to them in a network diagram and to indicate which of those individuals provided support. The mother's relationship with her husband and with the infant's maternal grandparents, mother's well-being in terms of affect and life satisfaction, and infant temperamental difficulty and infant–mother attachment security were assessed. Results reveal that mothers reported an average of 13 persons in their networks, but support was provided primarily by the husband, followed by the infant's maternal grandmother (particularly when there was more than 1 child), and 1 or 2 other family members and friends. Maternal affect and life satisfaction were related to infant difficulty and to support from and satisfaction with the spouse. Negative maternal affect was related to anxious/resistant attachment. Results affirm the importance of spousal support for mothers of infants in intact families. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessment of danger to themselves and their infants by rhesus macaque (Macaca mulatta) mothers.

This study investigated whether rhesus macaque (Macaca mulatta) mothers distinguish between what is dangerous to themselves and what is dangerous to their infants. The behavioral interactions between 11 mother–infant pairs and other females living in their group were analyzed in the 1st 2 mo of infant life. Mothers behaved as if they perceived higher ranking females as dangerous to both themselves and their infants, lower ranking females as dangerous to their infants but not to themselves, and their young daughters as relatively harmless to both themselves and their infants. Changes in maternal intolerance of infant handling between the 1st and 2nd mo covaried with changes in the probability of infant harassment rather than with the temporal pattern of aggression received by mothers. The possible cognitive mechanisms underlying parental recognition of infant's special needs are discussed in the light of comparative evidence from other mammalian species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.     

Infant attractiveness predicts maternal behaviors and attitudes.

The relations between infant attractiveness and maternal behavior were examined by observing mothers feeding and playing with their firstborn infants while they were still in the hospital after giving birth (N?=?144) and again when the infants were 3 months of age (N?=?115). The attitudes of the mothers toward their infants were also assessed. Mothers of more attractive infants were more affectionate and playful compared with mothers of less attractive infants. In contrast, the mothers of less attractive infants were more likely to be attentive to other people rather than to their infant and to engage in routine caregiving rather than affectionate behavior. The attitudes of the mothers of less attractive infants were also more negative than those of mothers of more attractive infants, but the number of differences in attitudes was not as great as the behavioral differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal immunization against viral disease

The protective effect of maternal antibody against many viral diseases has been recognized. The use of maternal immunization has been considered as a means to augment this protection in the young infant against disease. Advantages of maternal immunization include the fact that young infants are most susceptible to infections but least responsive to vaccines, that pregnant women are accessible to medical care and respond well to vaccines, that IgG antibodies cross the placenta well during the third trimester, and that immunization of the pregnant woman has the potential to benefit both the mother and the infant. Disadvantages include the potential inhibition of an infant's response to active immunization or natural infection and liability issues with pharmaceutical companies and physicians. Immunization of pregnant women with viral vaccines for poliovirus, influenza viruses, and rubella has been described and maternal vaccination with these vaccines has been found to be safe for both the mother and the fetus. An open-label study of post-partum women immunized with the purified fusion protein of RSV (PFP-2, Wyeth-Lederle Pediatrics and Vaccines, Inc., Pearl River, NY) demonstrated that the vaccine was non-reactogenic and immunogenic; RSV-specific antibody was detected in breast milk. Immunization of pregnant women with purified protein or subunit vaccines could be considered against neonatal viral pathogens, such as respiratory syncytial virus, parainfluenza viruses, herpes group viruses, and human immunodeficiency virus. Further studies are needed to define the safety and efficacy of maternal immunization.     

The guinea pig as a model for the study of maternal immunization against respiratory syncytial virus infections in infancy

Maternal immunization might protect infants from severe disease due to respiratory syncytial virus (RSV). Guinea pigs are susceptible to infections with RSV and transfer antibodies to their offspring prenatally. Pregnant guinea pigs were immunized by infection with RSV and their offspring were challenged intranasally with RSV. Pulmonary viral replication was compared among the pups born to immunized mothers (group A) and the pups from nonimmune mothers (group B) in two studies. Mean (+/-SD) log10 virus titers were, in study 1, group A, 2.3 +/- 0.8 pfu/g of lung (n = 10); group B, 3.6 +/- 1.5 pfu/g (n = 13) (P = .0058); and study 2, group A, < 1.69 pfu/g (n = 8); group B, 3.4 +/- 0.9 pfu/g (n = 6) (P = .0002). Thus, immunization of pregnant guinea pigs resulted in a significant reduction in viral replication in the lungs of their offspring. Guinea pigs should be useful for the study of maternal immunization against RSV.     

Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization

OBJECTIVE: To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria, pertussis, tetanus, and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth. DESIGN: Randomized study of infants born to mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg). SETTING: Three large city hospitals and one rural area providing prenatal care and obstetric services. SUBJECTS: Eighty neonates of HBsAg- and HBeAg-positive carrier mothers received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine (10 micrograms) at 0, 1, 2, and 11 months of age (group A) or at 3, 4, 5, and 11 months of age concomitant with diphtheria, pertussis, tetanus, and polio immunization (group B). A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months. MAIN OUTCOME MEASURES: Blood samples were collected at 0, 3, 6, 11, and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg. Follow-up visits were scheduled annually up to 5 years of age. RESULTS: Eight infants were excluded from analysis. During the study period, six children became HBsAg carriers, three in each group, which corresponds to a 5-year incidence of infection of 9% and 8% for groups A (three of 35) and B (three of 37), respectively. Subclinical infections (persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc) were encountered in another eight infants (four in each group). CONCLUSION: Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age.     

Immunity status against poliomyelitis in persons 13-14 years old living in Rome

The immunity against poliomyelitis in 1000 subjects 13-14 years old was evaluated. Neutralizing antibodies against poliovirus type 1, 2 and 3 were detected in 97.6%, 95.8% and 70% of samples, respectively. 3/1000 (0.3%) subjects were simultaneously seronegative to the three types. WHO does not suggest a protective level of International Units (IU), but our data indicate that such level is 0.45 IU for polio type 1, 0.65 IU for the type 2 and 0.138 for the type 3. A booster dose of vaccine in adolescence to ensure personal and herd immunity is recommended.     

Impact of premature birth on the development of the infant in the family.

This article describes effects of the birth of a premature infant on the family system and focuses on how problems associated with premature birth such as infant illness, hospitalization, and immaturity can place the family at risk. New data are presented describing differences in the behavior of preterm and full-term infants and in the feelings of mothers toward their infants at 12 months. Mothers of preterm infants reported feeling overprotective toward them, were less willing to leave them with sitters, and believed that their birth had an initially negative effect on the family. Preterm infants showed less exploratory play and stayed closer to their mothers during free play. The fact that these differences are not reflected in patterns of attachment, a key measure of the mother–infant relationship, is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)