Maternal Vaccination Research Articles

462. Infant antibody titers at birth following maternal COVID-19 vaccination and protection against infection in the first 6 months of life

Abstract Background Maternal vaccination is a promising strategy to prevent COVID-19 in early infancy, yet the amount of protection that maternally derived vaccine specific SARS-CoV-2 binding and neutralizing antibodies provide to infants in the first six months of life is not well characterized. Methods Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of an mRNA COVID-19 vaccine (primary series or boosted group, respectively) were followed prospectively from birth up to 6 months. At delivery, anti-Spike IgG and pseudovirus neutralizing antibody (Nab) levels were measured. Between September 2021 and December 2022, at pre-specified timepoints, COVID-19 infection was determined by verified maternal report. The risk reduction for COVID-19 in infants by antibody titers at delivery was estimated using a calendar-time Cox regression model after adjusting for maternal age, booster status, and recency of last dose. The relative vaccine effectiveness (VE) of 3 vs 2 maternal vaccine doses for COVID-19 in infants < 6 months was estimated in separate models. Results Infants in the boosted group (n=181) had higher anti-Spike IgG and pseudovirus Nab titers at delivery compared with the primary series group (n=260) (mean 4443 vs 1091 BAU/ml and 1567 vs 404 IC50, respectively; both p< 0.001). A 10-fold increase in anti-Spike IgG measured at delivery was associated with a 69.2% (95% CI: 38.1%, 84.6%, p=0.001) reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. Similarly, having a pseudovirus Nab response above an IC50 of 20 at delivery was associated with a 96.2% (95% CI: 75.1%, 99.4%; p=0.001) reduction in the infant’s risk of acquiring COVID-19 in the first 6 months. The relative VE of 3 vs 2 doses against infant COVID-19 was 65% (95% CI: 24%, 84%) when accounting for changes in anti-Spike IgG levels, and 83% (95% CI: 43%, 95%) when accounting for pseudovirus Nab levels. Conclusion Higher SARS-CoV-2 IgG Spike and pseudovirus Nab titers at delivery are associated with a substantially reduced risk of COVID-19 infection for infants in the first 6 months of life. Until infants are age-eligible for COVID-19 vaccination, maternal vaccination provides transplacentally transferred passive binding and neutralizing SARS-CoV-2 antibodies that protect against infection during early infancy. Disclosures Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Mark J. Mulligan, M.D., Lilly: Grant/Research Support|Meissa Vaccines, Inc.: Advisor/Consultant|Meissa Vaccines, Inc.: Board Member|Merck: Advisor/Consultant|Merck: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support Lalitha Parameswaran, MD, MPH, Pfizer: Grant/Research Support Richard M. Novak, MD, Moderna: Advisor/Consultant Rebecca C. Brady, MD, AztraZeneca: Grant/Research Support|PATH: Grant/Research Support|Pfizer: Grant/Research Support Bryan J. Berube, PhD, HDT Bio Corp.: Author on patents|HDT Bio Corp.: Salary|HDT Bio Corp.: Ownership Interest Barbra A. Richardson, PhD, Gilead Sciences: Advisor/Consultant Kathy M. Neuzil, MD, MPH, NIH: Grant/Research Support|Pfizer: Grant/Research Support Elizabeth R. Brown, ScD, Merck: Advisor/Consultant

1633. Willingness to receive maternal RSV vaccine and infant monoclonal RSV antibody

Abstract Background RSV results in substantial morbidity among young infants. Maternal RSV vaccines and monoclonal antibodies against RSV for infants have been developed, but little is known about acceptance of these products. Methods We conducted an online survey of U.S. adults who were pregnant (50%) or < 12 months postpartum (50%) between December 21, 2022 and January 2, 2023. Primary outcomes in two logistic regression models were willingness to receive RSV vaccine during pregnancy (definitely or probably would) and willingness to give their infant RSV monoclonal antibody. Covariates included prior vaccinations, vaccine attitudes, RSV risk perceptions, and RSV knowledge. Results Among respondents (N=523), mean age was 32 years (SD + 8 years); 48% had a high school education or less. In the last 12 months, 56% had received a COVID-19 vaccine and 58% an influenza vaccine; 66% had received Tdap during the pregnancy or intended to. A third of respondents thought their infant would get RSV in the first year of life; 14% thought severe illness would result. Sixty-one percent were willing to receive maternal RSV vaccine and 70% were willing for their infant to receive monoclonal antibody; 74% expressed willingness for at least one of these products. Predictors of maternal RSV vaccine willingness were Tdap during pregnancy (adjusted Odds Ratio [aOR] 2.83; 95% CI 1.75, 4.59), influenza vaccine in last 12 months (aOR 1.63; 95% CI 1.01, 2.63), positive feelings towards vaccines (aOR 4.15; 95% CI 2.49, 6.91), and higher perceived likelihood of their infant getting RSV illness (aOR 2.42; 95% CI 1.43, 4.09). Predictors of infant monoclonal antibody willingness were Tdap during pregnancy (aOR 2.50; 95% CI 1.52, 4.11), positive feelings towards vaccines (aOR 2.52; 95% CI 1.49, 4.26), and higher perceived likelihood of RSV illness (aOR 3.57; 95% CI 1.95, 6.53); living in the South versus Northeast was associated with lower willingness (aOR 0.41; 95% CI 0.20, 0.84). Conclusion Most respondents (74%) were willing to receive RSV vaccine and/or give their infant RSV monoclonal antibody. Receiving Tdap during pregnancy, favorable attitudes to vaccines, and higher perceived likelihood of RSV illness were associated with willingness for these products, which may inform future roll-out. Disclosures All Authors: No reported disclosures

478. COVID-19 maternal antibody concentrations in twin infants: impact of multiple pregnancy on transplacental antibody transfer during pregnancy

Abstract Background COVID-19 vaccines in pregnancy protect both pregnant individuals and young infants from severe illness via transplacental transfer of maternally-derived IgG. However, the impact of multiple (e.g. twin) pregnancy on transplacental transfer of SARS-CoV-2 IgG is unknown. We aimed to evaluate anti-Spike (S) antibody transfer among infants from twin pregnancies compared to singleton pregnancies. Methods We conducted a prospective cohort study among individuals with twin and singleton pregnancies who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery. We tested paired maternal and cord samples for anti-S IgG and used linear regression to evaluate associations between multiple or singleton pregnancy and anti-S antibody. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age (< 10th percentile) birthweight. Results We tested maternal/cord anti-S IgG from 25 twin and 291 singleton pregnancies. The median gestational age at delivery was 36 weeks for twin infants compared to 39 weeks for singleton infants. Median maternal anti-S IgG was 5812 BAU/mL (IQR:754, 16061) and 2971 BAU/mL (IQR:706, 14000) for twin and singleton pregnancies, respectively. Median cord anti-S IgG was 4110 BAU/mL (IQR: 527, 15937) and 3636 BAU/mL (IQR: 1019, 15465) for twin and singleton infants, respectively (Figure 1). Cord:maternal IgG ratios were significantly lower in twin pregnancies compared to singleton pregnancies (p < 0.01; Figure 2). After adjustment for covariates, there was no difference between maternal anti-S IgG concentrations (beta: -0.54; 95% confidence interval [CI]: -1.26,0.18; p=0.14), cord anti-S IgG concentrations (beta: -0.77; 95% CI: -1.68,0.13; p=0.10) or cord:maternal IgG ratios (beta: -0.07; 95% CI: -0.32,0.19; p=0.61) between twin and singleton pregnancies. Conclusion Twin and singleton infants benefit similarly from maternal COVID-19 vaccine during pregnancy. Higher risk pregnancies including multiple pregnancies should be considered in health policy discussions regarding COVID-19 vaccine timing in pregnancy. Disclosures Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

1942. Potential Public Health Impact of Bivalent Respiratory Syncytial Virus Prefusion F (RSVpreF) Maternal Vaccine for Prevention of RSV among US Infants

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI) among young children. A bivalent stabilized prefusion F subunit vaccine (RSVpreF) for pregnant people to protect their infants against RSV-LRTI is currently under review by the US Food and Drug Administration. We evaluated the potential public health impact, measured as the reduction in clinical outcomes and economic costs, of maternal vaccination with RSVpreF for the prevention of RSV-LRTI among US infants. Methods A cohort model was employed to depict clinical outcomes and economic costs of RSV-LRTI from birth to age 1 year, lifetime consequences of premature death, and impact of maternal vaccination with RSVpreF among infants. Clinical outcomes were projected (monthly) based on infant age, gestational age in weeks (wGA) at birth, RSV disease and fatality rates, and mother’s vaccination status, and included cases of medically attended RSV-LRTI and RSV-LRTI deaths. Vaccine effectiveness was derived from interim trial analyses and was assumed to vary by clinical presentation (hospital vs. ambulatory), timing of vaccine administration relative to birth, and wGA at birth. Economic costs were generated based on cases and corresponding unit costs. The public health impact of RSVpreF was evaluated assuming year-round use and 100% uptake. Results Without use of maternal RSVpreF vaccine, 48,246 hospitalizations, 144,495 emergency department (ED) encounters, and 399,313 outpatient clinic (OC) visits are projected to occur annually among the US birth cohort of 3.7M infants aged < 12 months. Maternal vaccination with RSVpreF resulted in a reduction of 24,520 hospitalizations, 45,957 ED encounters, and 128,745 OC visits, corresponding with a decrease in direct medical costs equal to $691.8 million and indirect (non-medical) costs equal to $110.0 million (Table).Table.Clinical outcomes and economic costs among US infants aged <1 year with maternal use of RSVpreF vaccine versus no intervention Conclusion Results from this evaluation indicate that maternal vaccination with RSVpreF would substantially reduce the clinical and economic burden of RSV-LRTI in infants. These results may be conservative as we did not include potential for reductions in outcomes such as maternal RSV disease, household transmission, and long-term sequelae such as asthma. Disclosures Ahuva Hanau, BS, Pfizer Inc.: Grant/Research Support Kimberly M. Shea, Ph.D., M.P.H., Pfizer: Employment|Pfizer: Stocks/Bonds Derek Weycker, Ph.D., Pfizer Inc.: Grant/Research Support Mark Atwood, MS, Pfizer Inc.: Grant/Research Support Erin Quinn, BS, Eisai Inc.: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|GRAIL: Advisor/Consultant|Pfizer Inc.: Advisor/Consultant|Santen Pharmaceutical: Advisor/Consultant Emily Kutrieb, B.A., Pfizer Inc.: Advisor/Consultant Jessica E. Atwell, PhD, MPH, Pfizer: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Bradford D. Gessner, M.D, M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Sarah J. Pugh, PhD, MPH, Pfizer Inc: Salary|Pfizer Inc: Stocks/Bonds Amy W. Law, PharmD, Pfizer: Employment|Pfizer: Stocks/Bonds

1624. SARS-CoV-2 Maternal Vaccination Induces More Efficient Placental Antibody Transfer to Newborns than SARS-CoV-2 Infection During Pregnancy

Abstract Background Passive immunization via maternal antibodies (Ab) is a key mechanism for infant protection in early life. This study analyzed the landscape of passive immunization induced by SARS-CoV-2 infection and/or vaccination by comparing the magnitude and durability of the transferred Ab. Methods Prospective multicenter observational cohort study of SARS-CoV2-infected and/or vaccinated pregnant women and their infants. We collected maternal and cord blood samples at delivery and neonatal/infant samples at delivery, and at 1, 2, 6 and 12 months (mo) of age. RBD and Spike IgG Ab titers were measured by ELISA. Results 215 mothers (infected=106, vaccinated=67, infected and vaccinated=42) and 174 infants (n=87, n=54, n=33, respectively) were enrolled. At birth RBD Ab titers median [IQR] of infants from vaccinated mothers [4.28 (3.48-4.80)] log10 ng/ml and from infected and vaccinated mothers [4.61 (4.27-4.93)] log10 ng/ml were higher than those from infected mothers [2.20 (0.10-3.30)] log10 ng/ml, p< 0.001. These differences were observed until 6 mo of age, when only 1/13 (7.7%) infant from infected mothers had detectable maternal Ab compared to 14/15 (93.3%) and 8/8 (100%) from the vaccinated, and infected and vaccinated groups, respectively. At 12 mo none of the infants born to infected mothers had detectable maternal Ab, while in the vaccinated group (n=11), 3 (27.3%) had persistent Ab, and 4 (36.4%) suspected infection. At 12 mo in the infected and vaccinated group (n=6) 3 had no Ab, and 3 had suspected infection. The median [IQR] placental Ab transfer ratio was higher in the vaccinated only group (2.94 [1.34-3.74]) than the infected only group (1.19 [0.33-2.52]) p< 0.01. Linear regression analyses demonstrated that the mean RBD Ab transfer ratio for infants from vaccinated vs infected women was 1.76 (95% CI=1.07-2.88, p=0.025) higher after adjusting for trimester of infection or vaccination. Similar results were observed with Spike Ab. Demographic and clinical characteristics of the study population m; median. IQR; interquartile range. N/A; not applicable. Figure 1. Comparison of RBD antibody titers in infected, vaccinated and infected and vaccinated groups at the time of delivery (from maternal blood, cord blood and neonatal blood) and at months 1, 2, 6 and 12 from neonatal/infant blood. Figure 2. Correlation between maternal and neonatal RBD antibody titers in groups of infected, vaccinated and infected and vaccinated mothers. These correlations also represent the values of the antibody transfer ratios across the placenta. While the bisector (red line) represents the values for a transfer ratio (TR) = 1, all values above it would correspond with TR>1 and those below with TR < 1. Green dots represent the infected group, the blue dots the vaccinated group, and the orange dots the infected and vaccinated group. Conclusion Infants from vaccinated mothers demonstrated maternal Ab up to 6 mo with higher titers than infants born from infected mothers. Antibodies generated by vaccination were transferred more efficiently than those generated by infection regardless of the trimester in which occurred. Disclosures Asuncion Mejias, MD, PhD, MsCS, Astra-Zeneca: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant Octavio Ramilo, MD, AstraZeneca: Honoraria|Bill & Melinda Gates Foundation: Grant/Research Support|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria

Immunomodulation of Antibody Glycosylation through the Placental Transfer

Establishing an immune balance between the mother and fetus during gestation is crucial, with the placenta acting as the epicenter of immune tolerance. The placental transfer of antibodies, mainly immunoglobulin G (IgG), is critical in protecting the developing fetus from infections. This review looks at how immunomodulation of antibody glycosylation occurs during placental transfer and how it affects fetal health. The passage of maternal IgG antibodies through the placental layers, including the syncytiotrophoblast, stroma, and fetal endothelium, is discussed. The effect of IgG subclass, glycosylation, concentration, maternal infections, and antigen specificity on antibody transfer efficiency is investigated. FcRn-mediated IgG transport, influenced by pH-dependent binding, is essential for placental transfer. Additionally, this review delves into the impact of glycosylation patterns on antibody functionality, considering both protective and pathological effects. Factors affecting the transfer of protective antibodies, such as maternal vaccination, are discussed along with reducing harmful antibodies. This in-depth examination of placental antibody transfer and glycosylation provides insights into improving neonatal immunity and mitigating the effects of maternal autoimmune and alloimmune conditions.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection

Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Maternal Tdap and influenza vaccination uptake 2017-2021 in the United States: Implications for maternal RSV vaccine uptake in the future

BackgroundAssessment of maternal vaccine coverage is important for understanding and quantifying the impact of currently recommended vaccines as well as modeling the potential impact of future vaccines. However, existing data lack detail regarding uptake according to week of gestational age (wGA). Such granularity is valuable for more accurate estimation of vaccine impact. ObjectiveTo summarize contemporary maternal Tdap vaccination uptake, overall, yearly, and by wGA, and maternal influenza vaccination uptake, overall, by influenza observation year, immunization month, and delivery month, in the US. MethodsFemale patients 18-49 years of age with a pregnancy resulting in a live born infant (i.e., delivery) between 2017 and 2021 were selected from the Optum electronic health records (EHRs) database. Recently published gestational age algorithms were utilized to estimate wGA. ResultsOf 1,021,260 deliveries among 886,660 women between 2017-2021, 55.1% had Tdap vaccination during pregnancy; vaccine coverage varied slightly by year (2017: 56.6%; 2018: 55.2%; 2019: 55.2%; 2020: 54.7%; 2021: 52.1%). Most (64.4%) maternal Tdap vaccinations occurred 27-32 wGA; 79.5% occurred during the entire 10-week recommended vaccination window (27-36 wGA). In the evaluation of influenza vaccination uptake (n=798,113 deliveries; 714,841 women), 33.5% of deliveries had influenza vaccination during influenza observation years 2017-2021, most (73.0%) of which occurred during influenza peak activity months (October-January) with approximately one-quarter (27.0%) of vaccinations having occurred during the off-peak months, mostly in September. ConclusionsIn this large contemporary analysis of EHR data, uptake of Tdap vaccination during pregnancy was consistent with previously published estimates; notably, most vaccination occurred early in the recommended 27-36 wGA window. Maternal influenza vaccination uptake largely correlated with peak influenza activity months and not gestational age. These study findings may have important implications for estimating the potential uptake and impact of future maternal vaccines.

Interventions to Improve Knowledge, Attitudes, and Uptake of Recommended Vaccines during Pregnancy and Postpartum: A Scoping Review.

Tetanus, pertussis, influenza, and COVID-19 vaccines are recommended for the prevention of related morbidity and mortality during pregnancy and postpartum. Despite the established benefits of vaccination for prenatal and postnatal women, maternal vaccination is not universally included in routine antenatal programs, especially in low- and middle-income countries. Furthermore, the uptake of recommended vaccines among pregnant and postpartum women remains below optimum globally. This review aimed to map the evidence on interventions to improve knowledge, attitudes, and uptake of recommended vaccines among pregnant and postpartum women. We conducted a comprehensive and systematic search for relevant literature in PubMed, Scopus, Web of Science, EBSCOhost, and Google Scholar. Overall, 29 studies published between 2010 and 2023 were included in this review. The majority (n = 27) of these studies were from high-income countries. A total of 14 studies focused on the influenza vaccine, 6 on the Tdap vaccine, 8 on both influenza and Tdap vaccines, and only one study on the COVID-19 vaccine. Patient-centered interventions predominated the evidence base (66%), followed by provider-focused (7%), health system-focused (10%), and multilevel interventions (17%). Overall, the effect of these interventions on knowledge, attitudes, and uptake of maternal vaccines was variable.

Maternal mRNA COVID-19 Vaccination During Pregnancy and Delta or Omicron Infection or Hospital Admission in Infants: Test Negative Design Study

(BMJ. 2023;380:e074035) Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rates are higher in infants than in older children. Passive immunity has been shown to help prevent other infections, such as pertussis, in infants through the transfer of maternal antibodies following vaccination during pregnancy. SARS-CoV-2 antibodies are found to be present in breastmilk, umbilical cord blood, and infant serum specimens following maternal vaccination during pregnancy and infection, and emerging research suggests maternal COVID-19 vaccination reduces infant infection and hospital admission rates. This study aimed to determine whether maternal vaccination during pregnancy with 2 primary doses or 2 primary doses plus booster of the mRNA COVID-19 vaccine series reduces the infection of omicron and delta SARS-CoV-2 and hospital admission of infants within 6 months following delivery.

Group B Streptococcal Disease in Infants in Japan.

This review describes the epidemiology of group B Streptococcus (GBS) infection in infants in Japan and discusses unresolved issues and future perspectives. Guidelines for the prevention of vertical transmission in Japan were implemented in 2008. The incidence of early-onset disease in Japan has remained stable at approximately 0.10/1000 livebirths or less, which is lower than in Europe and North America. The incidence of late-onset disease is also low, but has increased over the last decade, with an estimated 0.29/1000 livebirths in 2020. National surveillance studies in 2011-2015 and 2016-2020 reported case fatality rates of 4.5% and 6.5% for early-onset disease and 4.4% and 3.0% for late-onset disease, respectively. Sequelae of neurodevelopmental impairments were considerably associated with infants who developed meningitis. Predominant neonatal invasive strains have remained in the following order of serotypes: III, Ia, Ib and V, for the past 30 years. Conversely, the predominant serotypes of maternal colonization strains markedly changed from serotypes VI and VIII around 2000 to serotypes Ia, Ib, III and V over the last decade. Recurrence rates among infants < 1-year-old were estimated to be 2.8%-3.7%, and preterm birth and antenatal maternal GBS colonization were risk factors for recurrence. Several unresolved issues remain. First, the exact disease burden remains unclear because Japan does not have a nationwide system to register all infants affected by invasive GBS disease, and even population-based surveys are limited to up to 10 of the 47 prefectures. Others include low adherence to prevention guidelines of vertical transmission and the development of strategies based on Japanese epidemiological evidence rather than the Center for Disease Control and Prevention guidelines. The effectiveness of introducing maternal vaccines in Japan, where the disease incidence is low, needs to be carefully verified.

Factors Associated with Early Versus Late Uptake of the COVID-19 Vaccine during Pregnancy over Time in Australia: A Population-Based Cohort Study.

Pregnant women are at an increased risk of hospitalisation, admission to the intensive care unit, mechanical ventilation, and death from SARS-CoV-2 infection. The aim of this study is to determine the predictive factors associated with COVID-19 vaccine uptake during pregnancy over time in a population with a high background uptake of maternal influenza and pertussis vaccination. This is a population-based, cohort study of all pregnant women who gave birth in Victoria, Australia between 1 July 2021 and 30 June 2022. Data from the Victorian Perinatal Data Collection were analysed using univariable and multivariable logistic regression. This study reports on 77,719 women who gave birth over a 12 month period, of whom 49,281 (63.4%) received a COVID-19 vaccine, 54,887 (70.6%) received an influenza vaccination and 63,594 (81.8%) received a pertussis vaccine by the time of delivery. Pregnant women aged >30 years (aOR 1.31 CI 1.27, 1.36), who had >=8 antenatal visits (aOR 1.08 CI 1.04, 1.12), and those who received influenza vaccine (aOR 1.23 CI 1.19, 1.28) were more likely to have received a COVID-19 vaccine. Those who smoked (aOR 0.7 CI 0.66, 0.74), were First Nations (aOR 0.83 CI 0.74, 0.93) and those who gave birth in public hospitals (aOR 0.65 CI 0.63, 0.68) were less likely to receive COVID-19 vaccine in the first 12 months of the rollout. Maternal age, smoking, parity and Indigenous status were factors associated with delayed and sustained lower coverage, even in a population with background maternal influenza and pertussis coverage of 70.6% and 81.8%, respectively.

Assessing the Presence of IgG Antibodies against Influenza Viruses in Neonates after Maternal Vaccination and Factors That May Affect the Transplacental Transfer.

Special populations, particularly pregnant women, are uniquely susceptible to infectious diseases due to alterations in their immunological, respiratory, and cardiovascular systems during gestation. Influenza infections during the perinatal period have been associated with more severe maternal and perinatal outcomes, underscoring the critical importance of vaccination data for pregnant women. According to the World Health Organization (WHO), all pregnant women and those of childbearing age should receive the inactivated influenza vaccine, irrespective of their pregnancy stage. This study aimed to elucidate factors influencing neonatal antibody presence following maternal influenza vaccination. Conducted through convenience sampling in Athens, Greece, this study involved 78 pregnant women who received flu vaccinations. The participants completed questionnaires covering demographics, obstetric history, attitudes toward influenza vaccination, and knowledge about the influenza virus and pregnancy vaccination. Blood samples were collected from 83 neonates to assess IgG antibody presence. Five of the surveyed women had twin pregnancies. The statistical analysis employed IBM SPSS-Statistics version 26.0. This study revealed the presence of positive influenza A and B antibodies in neonates following maternal immunization. Furthermore, it identified factors such as the gestational week and timing of vaccination during pregnancy that influenced the transfer of antibodies from mother to fetus. These findings offer valuable insights for healthcare professionals to provide informed recommendations on influenza vaccination during pregnancy and empower expectant mothers to make informed decisions about the benefits of immunization.

MRNA SARS-CoV-2 Vaccination Before vs During Pregnancy and Omicron Infection Among Infants

Infants younger than 6 months are at risk of severe SARS-CoV-2 infection. Data are lacking on the optimum timing for maternal vaccination and estimated effectiveness against Omicron variants, including XBB, for infants. To investigate maternal vaccination against Omicron variants, including XBB, and the association of vaccination timing during pregnancy vs prior to pregnancy and risks of SARS-CoV-2 infection among infants aged 6 months or younger. This population-based cohort study was conducted between January 1, 2022, and March 31, 2023. Singapore's national dataset was used to study infants born at greater than 32 weeks' gestation between January 1, 2022, and September 30, 2022. The study included infants whose parents had a confirmed SARS-CoV-2 infection from the date of birth up to 6 months of age. Of 21 609 infants born during this period, 7292 (33.7%) had at least 1 parent infected with SARS-CoV-2 before the age of 7 months. Statistical analysis was performed from April to July 2023. Infants' mothers were unvaccinated, vaccinated prior to pregnancy, or vaccinated with a messenger RNA (mRNA) SARS-CoV-2 vaccine during pregnancy. Infants were considered infected if they had a positive polymerase chain reaction test. Among 7292 infants included in this study, 4522 (62.0%) had mothers who were Chinese, 527 (7.2%) had mothers who were Indian, 2007 (27.5%) had mothers who were Malay, and 236 (3.2%) had mothers who were other ethnicity; 6809 infants (93.4%) were born at full term, and 1272 infants (17.4%) were infected during the study period. There were 7120 infants (97.6%) born to mothers who had been fully vaccinated or boosted as of 14 days prior to delivery. The crude incidence rate was 174.3 per 100 000 person-days among infants born to mothers who were unvaccinated, 122.2 per 100 000 person-days among infants born to mothers who were vaccinated before pregnancy, and 128.5 per 100 000 person-days among infants born to mothers who were vaccinated during pregnancy. The estimated vaccine effectiveness (VE) was 41.5% (95% CI, 22.8% to 55.7%) among infants born to mothers vaccinated during pregnancy. Infants of mothers who received vaccination prior to pregnancy did not have a lower risk for infection (estimated VE, 15.4% [95% CI, -17.6% to 39.1%]). A lower risk for Omicron XBB infection was only observed among mothers vaccinated with the third (booster) dose antenatally (estimated VE, 76.7% [95% CI, 12.8% to 93.8%]). In this population-based cohort study, maternal mRNA vaccination was associated with a lower risk of Omicron SARS-CoV-2 infection among infants up to 6 months of age only if the vaccine was given during the antenatal period. These findings suggest that mRNA vaccination during pregnancy may be needed for lower risk of SARS-CoV-2 infection among newborns.

Association of Maternal Inactivated COVID-19 Vaccination within 3 Months before Conception with Neonatal Outcomes.

There is limited available data addressing whether inactivated COVID-19 vaccination before conception is associated with adverse neonatal outcomes. This cohort study included all singleton live births at our center from March 1 to June 30, 2022. According to whether a maternal inactivated COVID-19 vaccination had been administered within 3 months before conception or not, neonates were identified as being in the vaccinated or unvaccinated group. Vaccination information and clinical characteristics were extracted for analysis. Furthermore, neonatal outcomes were analyzed and compared between these two groups in the present study. The cohort included 856 eligible newborns, of whom 369 were exposed to maternal vaccination before conception and 487 were unexposed newborns. No differences were observed in rates of preterm birth, newborns being small for gestational age, or neonatal intensive care unit admission between exposed and unexposed newborns. Furthermore, even after adjusting for social-economic status and maternal characteristics, there remained no significant differences in these neonatal outcomes. Our study revealed no statistically significant differences between newborns born to women who received inactivated vaccines prior to conception compared with those who did not receive any vaccinations. In addition, our study also highlights the importance of considering COVID-19 vaccination before conception.

Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of Respiratory Syncytial Virus disease among infants in Canada: a simulation study

The cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort, regardless of gestational age or other risk factors. Additionally, we evaluated the health benefits and cost-effectiveness of a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of infants at high risk, including those born preterm or with chronic conditions, with nirsevimab during the RSV season. We developed a discrete-event simulation model, parameterized with the data on medically-attended RSV infections among infants under one year of age from 2010 to 2019, including outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women, reflecting the 2021 census data for Ontario, Canada were evaluated over a follow-up time horizon of one year from birth. Taking into account the costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives. Using a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only infants at high risk of severe disease would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF vaccine, respectively. This combined strategy would reduce infant mortality by 76%-85%, comparable to a 78% reduction achieved through a nirsevimab-only program of the entire birth cohort. The PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants. Passive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season. This study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation.

Characterizing attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya: Key considerations for demand generation efforts for vaccine acceptance.

This study examined attitudes toward maternal RSV vaccines among pregnant and lactating persons in Kenya. First pregnancy was associated with higher vaccine hesitancy among pregnant and lactating people, and social norms were associated with higher vaccine hesitancy among lactating people. Understanding maternal RSV attitudes is critical for vaccine acceptance.

Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies.

Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and in vitro experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an in silico prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient's anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.

Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action.

Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.

Twitter discussions on breastfeeding during the COVID-19 pandemic

BackgroundBreastfeeding is a critical health intervention in infants. Recent literature reported that the COVID-19 pandemic resulted in significant mental health issues in pregnant and breastfeeding women due to social isolation and lack of direct professional support. These maternal mental health issues affected infant nutrition and decreased breastfeeding rates during COVID-19. Twitter, a popular social media platform, can provide insight into public perceptions and sentiment about various health-related topics. With evidence of significant mental health issues among women during the COVID-19 pandemic, the perception of infant nutrition, specifically breastfeeding, remains unknown.MethodsWe aimed to understand public perceptions and sentiment regarding breastfeeding during the COVID-19 pandemic through Twitter analysis using natural language processing techniques. We collected and analyzed tweets related to breastfeeding and COVID-19 during the pandemic from January 2020 to May 2022. We used Python software (v3.9.0) for all data processing and analyses. We performed sentiment and emotion analysis of the tweets using natural language processing libraries and topic modeling using an unsupervised machine-learning algorithm.ResultsWe analyzed 40,628 tweets related to breastfeeding and COVID-19 generated by 28,216 users. Emotion analysis revealed predominantly “Positive emotions” regarding breastfeeding, comprising 72% of tweets. The overall tweet sentiment was positive, with a mean weekly sentiment of 0.25 throughout, and was affected by external events. Topic modeling revealed six significant themes related to breastfeeding and COVID-19. Passive immunity through breastfeeding after maternal vaccination had the highest mean positive sentiment score of 0.32.ConclusionsOur study provides insight into public perceptions and sentiment regarding breastfeeding during the COVID-19 pandemic. Contrary to other topics we explored in the context of COVID (e.g., ivermectin, disinformation), we found that breastfeeding had an overall positive sentiment during the pandemic despite the documented rise in mental health challenges in pregnant and breastfeeding mothers. The wide range of topics on Twitter related to breastfeeding provides an opportunity for active engagement by the medical community and timely dissemination of advice, support, and guidance. Future studies should leverage social media analysis to gain real-time insight into public health topics of importance in child health and apply targeted interventions.