Seroprevalence of rubella antibodies and determinants of susceptibility to rubella in a cohort of pregnant women in Canada, 2008–2011

Long term control of rubella and congenital rubella syndrome relies on high population-level immunity against rubella, particularly among women of childbearing age. In Canada, all pregnant women should be screened so that susceptible new mothers can be offered vaccination for rubella before discharge. This study was undertaken to estimate rubella susceptibility in a cohort of pregnant women in Canada and to identify associated socio-economic and demographic factors. Biobanked plasma samples were obtained from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, in which pregnant women were recruited between 2008 and 2011. Socio-demographic characteristics and obstetric histories were collected. Second trimester plasma samples (n = 1,752) were tested for rubella-specific IgG using an in-house enzyme-linked immunosorbent assay. The percentage of women with IgG titers <5 IU/mL, 5–10 IU/mL, and ≥10 IU/mL were 2.3%, 10.1%, and 87.6%, respectively. Rates of seronegativity, defined as <5 IU/mL, were 3.1% in women who had no previous live birth and 1.6% in women who had given birth previously. Among the latter group, seronegativity was higher in women with high school education or less (adjusted OR (aOR) 5.93, 95% CI 2.08–16.96) or with a college or trade school diploma (aOR 3.82, 95% CI 1.45–10.12), compared to university graduates, and those born outside Canada (aOR 2.60, 95% CI 1.07–6.31). In conclusion, a large majority of pregnant women were found to be immune to rubella. Further research is needed to understand inequalities in vaccine uptake or access, and more effort is needed to promote catch-up measles-mumps-rubella vaccination among socioeconomically disadvantaged and immigrant women of childbearing age.     

Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy

BackgroundRubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo’s (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC’s historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country’s strategy for RCV introduction.MethodsA rubella antibody seroprevalence assessment was conducted using serum collected during 2008–2009 from 1605 pregnant women aged 15–46 years attending 7 antenatal care sites in 3 of DRC’s provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC.ResultsOverall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p = 0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p ⩽ 0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p = 0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS.ConclusionsIn the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15 years. However, approximately 10–20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9 months to 14 years of age as well as vaccination of women of child bearing age through routine services.     

Determining rubella immunity in pregnant Alberta women 2009–2012

Rubella IgG levels for 157,763 pregnant women residing in Alberta between 2009 and 2012 were analyzed. As there have been no reported cases of indigenous rubella infection in Canada since 2005, there has been a lack of naturally acquired immunity, and the current prenatal population depends almost entirely on vaccine induced immunity for protection. Rubella antibody levels are significantly lower in younger maternal cohorts with 16.8% of those born prior to universal vaccination programs (1971–1980), and 33.8% of those born after (1981–1990) having IgG levels that are not considered protective (<15 IU/mL). Analysis across pregnancies showed only 35.0% of women responded with a 4-fold increase in antibody levels following post-natal vaccination. Additionally, 41.2% of women with antibody levels <15 IU/mL had previously received 2 doses of rubella containing vaccine. These discordant interpretations generate a great deal of confusion for laboratorians and physicians alike, and result in significant patient follow-up by Public Health teams. To assess the current antibody levels in the prenatal population, latent class modeling was employed to generate a two class fit model representing women with an antibody response to rubella, and women without an antibody response. The declining level of vaccine-induced antibodies in our population is disconcerting, and a combined approach from the laboratory and Public Health may be required to provide appropriate follow up for women who are truly susceptible to rubella infection.     

Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of maternal pertussis antibodies to the newborn

Background and objectivesPertussis is currently an emerging public health concern in some countries with high vaccination coverage. It is expected that maternal pertussis immunization could provide newborn protection. We compared pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and post-vaccination) with respect to levels in the newborn at delivery in women vaccinated during pregnancy. We also estimated anti-PT titers at primary infant vaccination.MethodsObservational study of pregnant women vaccinated with Tdap (≥20 weeks gestation) and their newborns between May 2012 and August 2013. Anti-PT levels were determined by ELISA in maternal (pre- and post-vaccination) and newborn blood.ResultsPre-vaccination, post-vaccination maternal and newborn samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3) years. Median weeks of gestation at vaccination were 27.2 (Q1–Q3 21.7–30.8). Anti-PT (≥10 IU/ml) levels were found in 37.1% of maternal pre-vaccination samples (geometric mean titer (GMT) 7.9 IU/ml (95% CI 6.8–9.2)), 90.2% of post-vaccination samples (GMT 31.1 IU/ml (95% CI 26.6–36.3)) and 94.7% of newborns (GMT 37.8 IU/ml (95% CI 32.3–44.1)). The Lin concordance index between post-vaccination maternal and newborn samples was 0.8 (95% CI 0.8–0.9). Transplacental transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated anti-PT levels ≥10 IU/ml.ConclusionsThere was a high correlation between anti-PT levels in mothers and newborns, with higher levels in newborns, which should be sufficient to provide protection against pertussis during the first months of life. Vaccination of pregnant women seems to be an immunogenic strategy to protect newborns until primary infant immunization.     

Effects of prior influenza virus vaccination on maternal antibody responses: Implications for achieving protection in the newborns

BackgroundIn the US, influenza vaccination is recommended annually to everyone ≥6 months. Prior receipt of influenza vaccine can dampen antibody responses to subsequent vaccination. This may have implications for pregnant women and their newborns, groups at high risk for complications from influenza infection.ObjectiveThis study examined effects of prior vaccination on maternal and cord blood antibody levels in a cohort of pregnant women in the US.Study designInfluenza antibody titers were measured in 141 pregnant women via the hemagglutination inhibition (HAI) assay prior to receipt of quadrivalent influenza vaccine, 30 days post-vaccination, and at delivery (maternal and cord blood). Logistic regression analyses adjusting for age, BMI, parity, gestational age at vaccination, and year of vaccination compared HAI titers, seroprotection, and seroconversion in women with versus without vaccination in the prior year.ResultsCompared to those without vaccination in the previous year (n = 50), women with prior vaccination (n = 91) exhibited higher baseline antibody titers and/or seroprotection rates against all four strains after controlling for covariates. Prior vaccination also predicted lower antibody responses and seroconversion rates at one month post-vaccination. However, at delivery, there were no significant differences in antibody titers or seroprotection rates in women or newborns, and no meaningful differences in the efficiency of antibody transfer, as indicated by the ratio of cord blood to maternal antibody titers at the time of delivery.ConclusionIn this cohort of pregnant women, receipt of influenza vaccine the previous year predicted higher baseline antibody titers and decreased antibody responses at one month post-vaccination against all influenza strains. However, prior maternal vaccination did not significantly affect either maternal antibody levels at delivery or antibody levels transferred to the neonate. This study is registered with the NIH as a clinical trial (NCT02148874).     

Sero-prevalence of rubella among pregnant women in India, 2017

BackgroundWe conducted a sero-survey among pregnant women attending antenatal clinics of six hospitals which also function as sentinel sites for CRS surveillance, to estimate the prevalence of IgG antibodies against rubella.MethodsWe systematically sampled 1800 pregnant women attending antenatal clinics and tested their sera for IgG antibodies against rubella. We classified sera as seropositive (titre ≥10 IU/ml), sero-negative (titre <8 IU/ml) or indeterminate (titre 8–9.9 IU/ml) per manufacturer's instructions. In a sub-sample, we estimated the titers of IgG antibodies against rubella. IgG titer of ≥10 IU/mL was considered protective.ResultsOf 1800 sera tested, 1502 (83.4%) were seropositive and 24 (1.3%) were indeterminate and 274 (15.2%) were sero-negative. Rubella sero-positivity did not differ by age group, educational status or place of residence. Three hundred and eighty three (87.8%) of the 436 sera had IgG concentrations ≥10 IU/mL.ConclusionThe results of the serosurvey indicate high levels of rubella sero-positivity in pregnant women. High sero-prevalence in the absence of routine childhood immunization indicates continued transmission of rubella virus in cities where sentinel sites are located.     

Mumps,measles and rubella vaccination in children with PFAPA syndrome

There is no published data regarding immunologic response to vaccinations in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis). The aim of this study was to evaluate mumps, measles and rubella immunity in children with PFAPA. 31 children with PFAPA syndrome and 22 healthy children (control group – CG) were recruited to the study. All children were previously vaccinated with one dose of MMR vaccine according to the Polish obligatory vaccination schedule. The patients from both groups were evaluated for anti-measles, anti-mumps and anti-rubella IgG antibodies concentrations (ELISA tests; the reference values for protective antibody levels were 150 IU/L, 16 RU/L and 11 IU/ml respectively). The percentage of patients with protective antibodies levels was as follows: measles – 93.55% of PFAPA and 95.45% of CG patients (p = 0.77); mumps – 74.19% of PFAPA and 95.45% of CG patients (p = 0.02); rubella – 80.65% of PFAPA and 90.9% of CG patients (p = 0.30). Conclusions: Children with PFAPA syndrome present a good response to the measles and rubella component of the MMR vaccine, however immunity against mumps after one dose of MMR may not be sufficient. Further investigation concerning immunity against vaccine-preventable diseases and the safety of vaccinations in children with periodic fever syndromes is required.     

Rubella seronegativity in antenatal screening – Is it influenced by the introduction of universal childhood rubella immunization?

ObjectiveThis study examined the impact of rubella immunization, implemented in Hong Kong in phases since 1978, on antenatal rubella serological status in Chinese women.MethodsIn a retrospective cohort study, the incidence of antenatal rubella seronegative status in our parturients managed from 1998 to 2013 was analyzed by their year-of-birth as follows: <1965 (no childhood immunization), 1965–1982 (single dose at Primary 6), and ≥1983 (two doses at age 12 months and 12 years), adjusting for other factors including age, parity, body mass index, place-of-birth status and hepatitis B surface antigen (HBsAg) status.FindingsRubella seronegativity decreased from 12.9%, 10.5%, to 9.8% respectively, and correlated inversely (P < 0.001) with year-of-birth cohorts. Despite similar demographic profiles, this correlation was found only in Hong-Kong-born women (from 12.6%, 7.5% to 6.5% respectively), who also had significant lower incidences of rubella seronegativity (OR 0.73, 0.31 and 0.29 respectively) and HBsAg seropositivity (OR 1.09, 0.63 and 0.48 respectively) than China-born women. On regression analysis, rubella seronegativity was actually significantly increased following the implementation of immunization (aOR 1.20) while it was the reverse for non-residents (aOR 0.61).ConclusionAlthough rubella seronegativity decreased with immunization, the effect was less than expected when adjusted for other risk factors.     

Reduced serologic sensitivity to influenza A virus illness among inactivated influenza vaccinees

We compared ≥4-fold increases in antibody titers by hemagglutination inhibition assay to RT-PCR results among 42 adults with PCR-confirmed influenza A virus illnesses. Serologic sensitivity was higher among unvaccinated (69%, 95% confidence interval [CI] = 48–90%) than vaccinated healthcare personnel (38%, 95% CI = 29–46%) in a 2010–11 prospective cohort.     

Immunization of pregnant women against pertussis: The effect of timing on antibody avidity

BackgroundThe Centers for Disease Control and Prevention recommend tetanus–diphteria–acellular pertussis (Tdap) immunization during pregnancy, preferably at 27–36 weeks gestation.AimsFirst, to assess the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) for newborns of women immunized with Tdap during late pregnancy as compared to unimmunized women. Second, to assess whether there is a preferential period of gestational Tdap immunization that provides the highest RAI of umbilical cord IgG to PT.MethodsRAI of IgG to PT was assessed via an adapted ELISA using NH₄SCN as a dissociating agent.ResultsWe found that newborns of women immunized with Tdap during late pregnancy (n = 52) had higher mean RAI of umbilical cord IgG to PT than those of unimmunized women (n = 8), 73.77% ± 12.08 (95% CI, 70.41–77.13) vs. 50.23% ± 21.32 (95% CI, 32.41–68.06), p < 0.001. Further, the RAI of umbilical cord IgG to PT was significantly higher in newborns of women immunized at 27–30⁺⁶ weeks gestation (n = 20) when compared with newborns of women immunized at 31–36 weeks (n = 22) and >36 weeks (n = 7), 79.53% ± 5.61 (95% CI, 76.91–82.16) vs. 71.56% ± 12.58 (95% CI, 65.98–77.14) vs. 63.93% ± 17.98 (95% CI, 47.31–80.56), p < 0.03.ConclusionGestational Tdap immunization between 27 and 30⁺⁶ weeks resulted in the highest avidity of IgG to PT conveyed at delivery as compared with immunization beyond 31 weeks gestation. Future studies should be conducted to confirm our findings to optimize pertussis-controlling strategies.     

Rubella specific cell-mediated and humoral immunity following vaccination in college students with low antibody titers

ObjectiveThis study measured cell-mediated immunity (CMI) and antibodies to clarify the basis of rubella reinfection after vaccination.MethodsIn a pool of 65 college students, 39 who exhibited hemagglutination–inhibition (HI) antibody titers against rubella of ≤1:16 were vaccinated with a rubella vaccine. The CMI was assessed with interferon-gamma release assay.ResultsThere was low correlation (r = 0.24) between the antibody titers and interferon-gamma levels at pre-vaccination status. Preexisting interferon-gamma levels were low in some subjects with low HI antibody titers of 1:8 and 1:16. Fifty-seven percent (4/7) of the subjects who were antibody-negative with past history of rubella vaccination at entry onto the study exhibited CMI. And 57% (4/7) of the subjects remained antibody-negative following a second vaccination, despite exhibiting CMI. HI antibody titers increased significantly after vaccination, whereas post-vaccination interferon-gamma levels did not exhibit significant increases. When subjects were divided (based on their past history of vaccination and antibody values) into natural infection and vaccination groups, HI antibody titers (mean ± SD) increased to 1:2^4.4 ± 1.4 from 1: 2^3.2 ± 0.4 (p = 0.065) in the natural infection group and to 1:2^4.4 ± 1.0 from 1:2^3.0 ± 0.8 (p < 0.00001) in the vaccination group following vaccination. The same classification revealed that interferon-gamma values did not increase significantly in either group following vaccination, but the interferon-gamma values at pre- and post-vaccination in the natural infection group were significantly higher than those at pre- and post-vaccination in the vaccination group (p < 0.05 and p < 0.05, respectively).ConclusionPre-vaccination interferon-gamma levels in each HI antibody titer group were similar. And there were some subjects with antibody-positive exhibited CMI-negative. These data may explain why rubella reinfection can occur in vaccinated seropositive individuals.     

Antenatal immunisation intentions of expectant parents: Relationship to immunisation timeliness during infancy

BackgroundMost women decide about infant immunisation during pregnancy. However, we have limited knowledge of the immunisation intentions of their partners. We aimed to describe what pregnant women and their partners intended for their future child's immunisations, and to identify associations between parental intentions and the subsequent timeliness of infant immunisation.MethodsWe recruited a cohort of pregnant New Zealand (NZ) women expecting to deliver between April 2009 and March 2010. The cohort included 11% of births in NZ during the recruitment period and was generalisable to the national birth cohort.We completed antenatal interviews independently with mothers and partners. We determined immunisation receipt from the National Immunisation Register and defined timely immunisation as receiving all vaccines (scheduled at 6-weeks, 3- and 5-months) within 30 days of their due date. We described independent associations of immunisation intentions with timeliness using adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsOf 6172 women, 5014 (81%) intended full immunisation, 245 (4%) partial immunisation, 140 (2%) no immunisation and 773 (13%) were undecided. Of 4152 partners, 2942 (71%) intended full immunisation, 208 (5%) partial immunisation, 83 (2%) no immunisation and 921 (22%) were undecided. Agreement between mothers and partners was moderate (Kappa = 0.42).Timely immunisation occurred in 70% of infants. Independent of their partner's intentions, infants of pregnant women who decided upon full immunisation were more likely to be immunised on time (OR = 7.65, 95% CI: 4.87 − 12.18). Independent of the future mother's intentions, infants of partners who had decided upon full immunisations were more likely to be immunised on time (OR = 3.33, 95% CI: 2.29 − 4.84).ConclusionsDuring pregnancy, most future parents intend to fully immunise their child; however, more partners than mothers remain undecided about immunisation. Both future mothers’ and future fathers’ intentions are independently associated with the timeliness of their infant's immunisations.     

Self-assessed health,perceived stress and non-participation in breast cancer screening: A Danish cohort study

ObjectivePopulation-based cancer screening is offered in many countries to detect early stages of cancer and reduce mortality. Screening efficiency and equality is susceptible due to a group of non-participants. We investigated associations between self-assessed health, perceived stress and subsequent non-participation in breast cancer screening.MethodsThis population-based cohort study included 4512 women who had participated in a Health Survey in 2006 and who were also the target group (aged 50–69 years) for the first organised breast cancer screening programme -3 years later in the Central Denmark Region in 2008–2009.ResultsA U-shaped association was observed for physical health assessment as women with the highest (PR = 1.28, 95% CI: 1.06–1.55), and the lowest (PR = 1.41, 95% CI: 1.18–1.68) physical health scores were less likely to participate in the programme than women with physical health scores in the middle range. Women with low mental health assessment were more likely not to participate than women with mental health scores in the middle range (PR = 1.44, 95% CI: 1.22–1.69). Higher non-participation propensity was also observed for women with the highest perceived stress scores (PR = 1.27, 95% CI: 1.07–1.51) compared with women scoring in the middle range.ConclusionsWomen with highest and lowest self-assessed physical health, with lowest mental health or highest perceived stress were significantly more likely not to participate in breast cancer screening 2 -3years later than women who reported average health. Interventions targeting these groups may promote equal participation in future breast cancer screening programmes.     

Healthy excessive weight in Portuguese women 4 years after delivery of a liveborn

ObjectiveTo quantify the prevalence of healthy excessive weight and determinants of metabolic profile, considering women's reproductive life.MethodsWe evaluated 1847 mothers of a birth cohort assembled after delivery and reevaluated 4 years later. A healthy profile was defined as the absence of hypertension, diabetes, dyslipidemia, C-reactive protein < 3 mg/l and being below the second tertile of HOMA-IR. Adjusted odds ratios (OR) and confidence intervals (95% CI) were computed using multinomial logistic regression, taking women with normal BMI as the reference category of the outcome.ResultsFour years after delivery, 47% of women had normal BMI, 33% were overweight and 20% obese. In each BMI class, 61%, 33% and 12% presented a healthy metabolic profile, respectively. Family history of CVD/cardiometabolic risk factors was associated with a higher probability of obesity with a not healthy metabolic profile (OR = 1.39 95% CI: 0.98–1.98). Women who breastfed the enrolled child for > 26 weeks and practiced physical exercise were less likely to be obese and metabolically unhealthy (OR = 0.39 95% CI: 0.23–0.68; OR = 0.48 95% CI: 0.33–0.70, respectively), with no effect on healthy excessive weight.ConclusionsThese results support the existence of a healthy excessive weight phenotype in women after motherhood, influenced by anthropometrics, genetic and lifestyles characteristics.     

Changes in cervical cancer incidence following the introduction of organized screening in Italy

ObjectiveTo quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs.MethodsThis population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25–74 years in 1995–2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium.ResultsICC incidence rates diminished with time since OCSPs full-activation: after 6–8 years, the IRR was 0.75 (95% CI: 0.67–0.85). The reduction was higher for stages IB–IV (IRR = 0.68, 95% CI: 0.58–0.80), squamous cell ICCs (IRR = 0.74, 95% CI: 0.64–0.84), and particularly evident among women aged 45–74 years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25–44 years (IRR = 1.34, 95% CI: 0.91–1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%).Conclusion(s)Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.     

Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age

Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data.In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix^®) during pregnancy (vaccine group) or received no vaccine (control group).All infants were vaccinated with Infanrix Hexa^® according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT) and diphtheria toxoid (DT) were measured using commercially available ELISA tests. Antibody levels were expressed in International Units per milliliter.Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG (p = 0.003) and anti-DT IgG (p = 0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG (p = 0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose.The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting effect is yet unknown.Clinicaltrials.gov identifier: NCT01698346.     

Evaluation of measles–rubella vaccination for mothers in early puerperal phase

BackgroundThe postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella.MethodsA prospective study of measles–rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤1:4 on the neutralization test [NT]) or rubella (≤1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk.ResultsOf the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0–13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9–76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P = 0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants.ConclusionMR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu.     

Specific memory B cell response and participation of CD4+ central and effector memory T cells in mice immunized with liposome encapsulated recombinant NE protein based Hepatitis E vaccine candidate

BackgroundLiposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys.MethodsThe current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420 days post immunization (PI) with 5 μg rNEp encapsulated in liposome based adjuvant (2 doses, 4 weeks apart). Mice immunized with a lower dose (1 μg) were assessed only for anamnestic response post booster dose.ResultsVaccine candidate immunized mice (5 μg dose) elicited strong anti-HEV IgG response that was estimated to persist for lifetime. At day 120 PI, frequency of memory B cells was higher in immunized mice than those receiving adjuvant alone. Anti-HEV IgG titers were lower in mice immunized with 1 μg dose. A booster dose yielded a heightened antibody response in mice with both high (>800 GMT, 5 μg) and low (⩽100 GMT, 1 μg) anti-HEV IgG titers. At day 6th post booster dose, HEV-specific antibody secreting plasma cells (ASCs) were detected in 100% and 50% of mice with high and low anti-HEV IgG titers, respectively, whereas the frequencies of CD4⁺ central and effector memory T cells were high in mice with high anti-HEV IgG titers only.ConclusionsTaken together, the vaccine candidate effectively generates persistent and anamnestic antibody response, elicits participation of CD4⁺ memory T cells and triggers memory B cells to differentiate into ASCs upon boosting. This approach of assessing the immunogenicity of vaccine candidate could be useful to explore the longevity of HEV-specific memory response in future HEV vaccine trials in human.