Maternal Vaccination Research Articles

Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.

Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

Calibration of a serum reference standard for Group B streptococcal polysaccharide conjugate vaccine development using surface plasmon resonance

Group B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality worldwide. Development of a maternal vaccine to protect newborns through placentally transferred antibody is considered feasible based on the well-established relationship between anti-GBS capsular polysaccharide (CPS) IgG levels at birth and reduced risk of neonatal invasive GBS. An accurately calibrated serum reference standard that can be used to measure anti-CPS concentrations is critical for estimation of protective antibody levels across serotypes and potential vaccine performance. For this, precise weight-based measurement of anti-CPS IgG in sera is required. Here, we report an improved approach for determining serum anti-CPS IgG levels using surface plasmon resonance with monoclonal antibody standards, coupled with a direct Luminex-based immunoassay. This technique was used to quantify serotype-specific anti-CPS IgG levels in a human serum reference pool derived from subjects immunized with an investigational six-valent GBS glycoconjugate vaccine.

Comparison of attitudes toward routine maternal vaccines and COVID-19 vaccines among pregnant patients in an urban safety-net setting

ObjectiveTo explore attitudes toward tetanus-diphtheria-acellular pertussis (Tdap), influenza, and COVID vaccines among English- and Spanish- speaking pregnant individuals in a safety net setting. MethodsPregnant people aged 18 years or older were recruited from outpatient clinics between August 2020 and June 2021. Interviews were conducted via phone in English or Spanish, recorded, transcribed, and translated verbatim. Data were qualitatively analyzed using modified grounded theory and content analysis. Results42 patients participated (22 English-speaking, 20 Spanish-speaking). Most participants expressed positive attitudes towards both routine prenatal vaccinations and COVID-19 vaccines, endorsing the belief that vaccines promote health and considering vaccines a social norm. Positive attitudes were similar for the three vaccines, and among Spanish- and English-speaking individuals. Participants trusted their healthcare provider's recommendations and felt comfortable receiving booster doses of vaccines they had received successfully in the past. Vaccine concerns differed by each vaccine. Despite limited knowledge, few participants expressed concerns about Tdap vaccines. Concerns around influenza vaccines often stemmed from personal experience and centered around ineffectiveness and increased risk of flu-like illnesses. Participants expressed the most concerns related to COVID vaccinations, including misinformation about serious side effects and distrust around accelerated approval of the vaccines. Many participants wished to know more about the side effects and safety of vaccinating during pregnancy, especially regarding the fetus's health. ConclusionsMost participants supported routine prenatal vaccinations, including COVID vaccines. Clinicians are trusted information sources and can help reinforce positive attitudes and social norms of receiving vaccinations in pregnancy while addressing vaccine-specific concerns. FundingThis work was supported by Suzanne Cutler Vaccination Education & Research Fund at the Boston University Chobanian and Avedisian School of Medicine for funding and support.

Standardizing case definitions for monitoring the safety of maternal vaccines globally: GAIA definitions, a review of progress to date.

In 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally-concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high-income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher-level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low- and middle-income settings, as well as the 13 that have not undergone any validation.

‘It has been the hardest decision of my life’: a mixed-methods study of pregnant women’s COVID-19 vaccination hesitancy

Objective To explore psychological factors influencing decision-making regarding COVID-19 vaccination among pregnant women. Design Cross-sectional mixed-methods online survey comprising sociodemographic factors, health beliefs, trust and anticipated regret, and open-ended qualitative questions. Pregnant respondents living in the UK or Ireland (n = 191) completed the online survey during June and July 2021. Main outcome measures Intention to vaccinate against COVID-19 during pregnancy, with response options yes (vaccine accepting), no (vaccine resistant), unsure (vaccine hesitant). Qualitative questions about perceived benefits and risks of COVID-19 vaccination during pregnancy. Results Multivariate analysis of correlates of vaccine hesitancy and resistance revealed independent associations for perceived barriers to the COVID-19 vaccine, anticipated regret, and social influences. Most respondents described making a decision regarding COVID-19 vaccination in the absence of satisfactory information or guidance from a health care professional. Vaccine hesitant and resistant respondents reported significantly greater barriers to the COVID-19 vaccination than vaccine accepting respondents. Concerns about the vaccine focussed on the speed of its development and roll-out and lack of evidence regarding its safe use in pregnancy. Conclusion Participants who did not intend to be vaccinated against COVID-19 in pregnancy focused on vaccine fears as opposed to virus fears. Results indicate that pregnant women need balanced vaccine information and unequivocal health care provider recommendation to aid maternal vaccination decision-making.

Adverse infant outcomes following low-risk pregnancies in England: a retrospective cohort study

BackgroundThere are limited data describing adverse infant outcomes in infants born to women with a low risk of complications during pregnancy, such as those who may be enrolled in maternal immunization trials. This retrospective study estimated incidence proportions of infant outcomes in different cohorts of liveborn infants in England between 2005 and 2017.MethodsThe incidence proportions of 10 infant outcomes were calculated for liveborn infants from pregnancies represented in the Clinical Practice Research Datalink (CPRD) Mother-Baby Link (MBL) and linkage to Hospital Episode Statistics (HES). Three infant cohorts were designed: (1) the all pregnancies infants cohort (N = 185,119), (2) the all pregnancies with a gestational age (GA) ≥ 24 weeks infants cohort (N = 183,869), and (3) the low-risk pregnancies infants cohort (LR infants cohort, N = 121,871), which included pregnancies with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA.ResultsThe most common adverse infant outcome in the three infant cohorts was macrosomia (e.g., 1,085.9/10,000 live births in the LR infants cohort), followed by minor congenital anomalies (e.g., 800.6/10,000 in the LR infants cohort), very low/low birth weight (e.g., 400.6/10,000 in the LR infants cohort), and major congenital anomalies (e.g., 270.4/10,000 in the LR infants cohort). The incidence proportions for early-onset sepsis, very low/low birth weight, and minor and major congenital anomalies were lower in the LR infants than in the other cohorts (non-overlapping confidence intervals [CIs]). The incidence proportions of neonatal death, infant death, late-onset sepsis, macrosomia, small for GA, and large for GA were similar between cohorts (overlapping CIs).ConclusionsThis study generated background rates of adverse infant outcomes from liveborn infants of all and low-risk pregnancies represented in the CPRD Pregnancy Register MBL and linkage to HES. The results indicate lower incidence proportions of several adverse infant outcomes in infants from low-risk pregnancies compared to all pregnancies, illustrating the importance of considering maternal risk factors. These background rates may facilitate the interpretation of safety data from maternal immunization trials and of pharmacovigilance data from maternal vaccines. They may also be of interest for other interventions studied in pregnant women.

A Plant-Derived Maternal Vaccine against Porcine Epidemic Diarrhea Protects Piglets through Maternally Derived Immunity.

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. PEDV belongs to the coronavirus family and is characterized by high levels of mutability. The primary goal of a PEDV vaccine is to provide immunity to newborn piglets through vaccination of sows. Plant-based vaccines are becoming more popular because they have low manufacturing costs, are easily scalable, have high thermostability, and a long shelf life. This is in contrast to conventional vaccines which include inactivated, live, and/or recombinant types that can be expensive and have limited ability to respond to rapidly mutating viruses. The binding of the virus to host cell receptors is primarily facilitated by the N-terminal subunit of the viral spike protein (S1), which also contains several epitopes that are recognized by virus-neutralizing antibodies. As a result, we generated a recombinant S1 protein using a plant-based vaccine platform. We found that the recombinant protein was highly glycosylated, comparable to the native viral antigen. Vaccination of pregnant sows at four and two weeks before farrowing led to the development of humoral immunity specific to S1 in the suckling piglets. In addition, we noted significant viral neutralization titers in both vaccinated sows and piglets. When challenged with PEDV, piglets born from vaccinated sows displayed less severe clinical symptoms and significantly lower mortality rates compared to piglets born from non-vaccinated sows.

Optimizing next-generation RSV prevention in Mali: A cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis.

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Socio-psychological determinants of second trimester maternal pertussis vaccination acceptance in the Netherlands.

A maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is offered to all pregnant women in the Netherlands in their second trimester since December 2019. However, former studies solely investigated the socio-psychological factors that influence vaccine acceptance among pregnant women in the third trimester. We identified predicting factors for attitude, intention and acceptance of maternal Tdap vaccination during the second trimester of pregnancy. As part of a large prospective cohort study, women early in pregnancy completed a questionnaire on determinants regarding acceptance of maternal Tdap vaccination between 20 and 24w of gestation. The vaccine was offered after completion of the questionnaire. A random forest model and Receiver Operating Characteristics (ROC) analyses were carried out to identify the factors most predictive for vaccine acceptance on the whole data set, and also in sensitivity analysis on a subset reflecting the annual nationwide 70% vaccination uptake. Among 1158 participants who were offered a Tdap vaccination between 20 and 24w of gestation, 1098 (94.8%) accepted and 60 (5.2%) rejected the vaccine. Random forest analyses identified intention as most predictive for acceptance, followed by attitude towards vaccination, beliefs regarding safety, risk perception of severity of side effects, moral responsibility, beliefs regarding effectiveness and risk perception of susceptibility of side effects, with a sensitivity of 100% and a specificity of 40%, for which this combination could be improved by the ROC analysis to 82% and 67%, respectively. The sensitivity analysis yielded an order of predictors that generally corresponded with the initial model. Intention, attitude, beliefs on safety and effectiveness, risk perception of side effects and moral responsibility were most predictive for maternal Tdap vaccine acceptance during the second trimester of pregnancy, in accordance with studies regarding third trimester vaccination. These should be discussed by healthcare professionals early in pregnancy to provide an informed choice towards vaccine acceptance.

A Descriptive Study of Maternal Vaccination Uptake, Attitudes, and Beliefs in Pregnancy Among Persons Delivering at an Urban Safety Net Hospital.

To estimate uptake of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines during pregnancy and describe vaccine attitudes and beliefs among predominantly racial and ethnic minority individuals delivering at a publicly funded hospital. We collected survey and electronic medical record data for English-speaking postpartum individuals who delivered a live-born infant from July 7, 2022, through August 21, 2022, and agreed to participate in our study. The 58-item survey included questions about general vaccine attitudes and beliefs as well as vaccine-specific questions. We calculated rates of influenza, Tdap, and COVID-19 vaccinations and compared distributions of survey responses by number (no vaccines, one vaccine, or two or three of the recommended vaccines) and type of vaccines received during pregnancy. Of the 231 eligible individuals, 125 (54.1%) agreed to participate. Rates of influenza, Tdap, and COVID-19 vaccination were 18.4%, 48.0%, and 5.6% respectively. A total of 61 (48.8%) did not receive any recommended vaccines during pregnancy, 40 (32.0%) received one vaccine, and 24 (19.0%) received two or three vaccines. Approximately 66.1% of the no vaccine group, 81.6% of the one vaccine group, and 87.5% of the two or three vaccine group strongly agreed or agreed that they trusted the vaccine information provided by their obstetrician or midwife. While most (>69.2%) agreed that the vaccine-preventable diseases were dangerous for pregnant women, only 24.0%, 29.3%, and 40.3% agreed that they were worried about getting influenza, whooping cough, or COVID-19, respectively, while pregnant. Vaccine uptake in our population was low and may be due, in part, to low perceived susceptibility to vaccine-preventable diseases. Obstetricians and midwives were trusted sources of vaccine information, suggesting that enhanced communication strategies could be critical for addressing maternal vaccine hesitancy, particularly in communities of color justifiably affected by medical mistrust.

Evaluating Ob-Gyn Resident Beliefs Toward COVID-19 Vaccine and Its Safety and Efficacy in Pregnancy: A National Survey [ID: 1375473

INTRODUCTION: Vaccination beliefs vary across the United States. The American College of Obstetricians and Gynecologists (ACOG) recently published formal recommendations for COVID-19 vaccination in pregnancy. Outlooks regarding maternal vaccination among obstetrician–gynecologists have important implications for maternal morbidity and mortality. Resident perception of COVID-19 vaccination has yet to be studied. Our national survey sought to evaluate ob-gyn resident views regarding COVID-19 vaccine safety and efficacy in pregnancy. METHODS: In April 2022, a national survey was sent to all Accreditation Council for Graduate Medical Education-accredited obstetrics and gynecology residency programs in the United States. Responses were obtained and descriptive analysis was performed. Institutional review board approval was obtained. RESULTS: The majority of ob-gyn residents believed that pregnant patients should be vaccinated against COVID-19 (96.1%, n=73). In the outpatient setting, most resident physicians reported that they strongly recommend the COVID-19 vaccine to pregnant patients (89.5%, n=68). The majority of respondents believed the COVID-19 vaccine is effective in reducing maternal morbidity and mortality (98.7%, n=75). Of that subgroup, a minority of respondents felt the safety profile of COVID-19 vaccine in pregnancy is unknown (10.7%, n=8). Geographic distribution of respondents, as defined by Centers for Disease Control and Prevention Census designations, were as follows: Midwest (34.3%, n=26); Northeast (40.8%, n=31); South (10.5%, n=8); West (14.4%, n=11). CONCLUSION: The majority of ob-gyn residents believed the COVID-19 vaccine to be effective in reducing maternal morbidity and mortality. Although a minority were uncertain regarding its safety profile, they continued to recommend vaccination per ACOG guidelines. While descriptive responses were homogenous, a paucity of respondents from the South and West regions made geographic distribution uneven.

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

Abstract Pregnancy is associated with a higher risk of adverse symptoms and outcomes for most infectious diseases, including SARS-CoV-2. These adverse risks are also observed in neonates. Antibodies provide protection against SARS-CoV-2 infection, and have been reported after maternal vaccination, maternal infection, and through passive transfer from mother to fetus in utero. However, it is unclear whether the magnitude or quality of maternally-derived fetal antibodies differs in the context of infection or vaccination. Here, 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 the greater New Orleans area. Histories of SARS-CoV-2 infection or vaccination were obtained. Humoral immunity 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. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies from naïve subjects. Importantly, 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. Supported by grants from NIH (NCI U54CA260581-02, NHLBI Grant HL-061007) and USDA (APHIS NBAF NSTP)

Comparison of Pregnancy and COVID-19 Complications Stratified by Maternal Vaccination Status [ID: 1363064

INTRODUCTION: COVID-19 vaccination has been shown to reduce disease severity. However, it is unclear how vaccination status may affect complications of both pregnancy and COVID. This study aims to determine whether maternal vaccination status affects COVID-19 and pregnancy complications. METHODS: This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 during the Alpha/Delta or Omicron wave (February 1, 2021 to April 1, 2022) at a single academic tertiary care center. Study was approved by the IRB. Women were divided into groups based on vaccination status. The primary outcome was COVID-19 complications (venous thromboembolism, stroke, myocardial infarction, pneumonia [PNA], acute respiratory failure [ARF], renal or hepatic failure, transaminitis). Pregnancy complications (pregnancy-induced hypertension, postpartum hemorrhage, fetal demise, preterm labor, blood transfusion, pyelonephritis, preterm prelabor rupture of membranes [PPROM]) and maternal characteristics were collected from chart review. Statistical analysis was performed using SPSS using chi-square tests and Student t tests with significance defined as P<.05. RESULTS: A total of 463 pregnant patients were included in this study. One hundred fifty-nine were fully or partially vaccinated, while 304 were not vaccinated. There was a significantly higher incidence of COVID-19 complications in patients who did not receive the vaccine (3.3%) compared to those who received the vaccine (0%) (P=.02). No patients who were vaccinated had PNA or ARF. Chronic hypertension and pregestational diabetes were also significantly associated with COVID complications. Vaccination status was not associated with any pregnancy complication. Incidence of preeclampsia without severe features was higher in vaccinated women (5.7 versus 1.6, P=.02). Of the patients who received the booster, 10.4% (5/48) had PPROM compared to 3.5% (13/372) who did not receive the booster (P<.05). CONCLUSION: Our data suggest that vaccination status is not related to obstetrical outcomes; however pregnant women who received the COVID-19 vaccine are protected from COVID-19 complications.

In silicooptimization of prenatal vaccine regimens to promote early-life immunity

Abstract Newborn children are vulnerable to infection due to their dampened humoral immune response. Maternal immunoglobulin G (IgG) transferred across the placenta provides passive immunity to newborns, and prenatal vaccination to boost pathogen-specific IgG transfer successfully reduced the incidence of neonatal tetanus, diphtheria, and acellular pertussis (Tdap) infections. Despite this, higher rates of infection among premature neonates signifies a deficiency in current immunization programs. To identify regulators of IgG transfer and refine prenatal vaccine regimens, we used a novel in silico approach. To disentangle the role of placental Fc gamma receptors (FcγRs) in IgG transfer, we conducted multiplexed immunofluorescence (mIF) to measure FcγR expression in paraffin-embedded placental tissue. A mechanistic model of placental IgG transfer informed by single cell RNA sequencing and the mIF data revealed FcγRIIb as a key driver of dynamic subclass-specific IgG transcytosis in placental endothelial cells (ECs). In model simulations and experiments in vitro with human umbilical vein ECs, we found the maternal IgG profile fine-tunes antigen- and subclass-specific IgG transfer dynamics. To identify immunization windows of opportunity for maximum IgG transfer, we simulated maternal vaccination by integrating a model of B cell activation and antibody production into the mechanistic model. This revealed first trimester vaccination as a potential strategy to maximize Tdap-induced IgG transport to premature newborns. We conclude that optimal prenatal vaccine regimens depend on gestational length and that novel prenatal vaccines can leverage these determinants of IgG transport to maximize neonatal immune protection. Supported by grants from NIH (T32 GM145443) the Jeffress Trust Awards Program.

The non-specific effects of maternal immunization on birth outcomes: The evidence, mechanisms, and the implications.

Preterm birth (PTB) and stillbirth remain two of the most important causes of death, morbidity, and disability in childhood. Despite efforts to reduce PTB and stillbirth worldwide, rates of these adverse outcomes remain persistently elevated, independent of income setting. There is an urgent need for more effective interventions to reduce associated neonatal and early childhood morbidity and mortality. Maternal vaccines are a well-established strategy used for prevention of pathogen-specific disease in mothers and infants through transplacental antibody transfer. Beyond these pathogen-specific benefits, some studies have also identified non-specific effects (NSEs) of maternal vaccination protecting against several adverse birth outcomes, including PTB and stillbirth. This paper will review the evidence supporting the NSEs of maternal vaccination on birth outcomes, describe the possible underlying mechanisms, outline the research gaps, and summarize the significance from a global health perspective.

Health Systems Determinants of Delivery and Uptake of Maternal Vaccines in Low- and Middle-Income Countries: A Qualitative Systematic Review.

Maternal vaccination is considered a key component of the antenatal care package for improving maternal and child health. Low- and middle-income countries (LMICs) fall short of global targets to prevent maternal and neonatal deaths, with a disproportionate burden of vaccine-preventable diseases. Strategies towards ending preventable maternal mortality necessitate a health systems approach to adequately respond to this burden. This review explores the health systems determinants of delivery and uptake of essential maternal vaccines in LMICs. We conducted a qualitative systematic review of articles on maternal vaccination in LMICs, published between 2009 and 2023 in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Thematic analysis was conducted to identify key themes in the literature, interpreted within a conceptual framing that explores the systems determinants influencing maternal vaccines. Our search yielded 1309 records, of which 54 were included, covering 34 LMICs. Most of the included studies were from South America (28/54) and included pregnant women as the primary study population (34/54). The studies explored influenza (25/54) and tetanus toxoid (20/54) vaccines predominantly. The findings suggest that systems hardware (lack of clear policy guidelines, ineffective cold-chain management, limited reporting and monitoring systems) are barriers to vaccine delivery. Systems software (healthcare provider recommendations, increased trust, higher levels of maternal education) are enablers to maternal vaccine uptake. Findings show that formulation, dissemination and communication of context-specific policies and guidelines on maternal vaccines should be a priority for decision-makers in LMICs.

Influence of Timing of Maternal Pertussis Immunization on the Avidity of Transferred Antibodies in Term and Preterm Neonates.

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

The economic burden of RSV-associated illness in children aged < 5 years, South Africa 2011–2016

BackgroundData on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated the cost of RSV-associated illness in fine age bands to allow more accurate cost-effectiveness models to account for a limited duration of protection conferred by short- or long-acting interventions.MethodsWe conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests, and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalizations or clinic visits; the PDE was multiplied by the number of days of care to provide a case cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged < 1 year and as a single group for children aged 1–4 years. We then applied our data to a modified version of the World Health Organization tool for estimating the mean annual national cost burden, including medically and non-medically attended RSV-associated illness.ResultsThe estimated mean annual cost of RSV-associated illness in children aged < 5 years was US dollars ($)137,204,393, of which 76% ($111,742,713) were healthcare system incurred, 6% ($8,881,612) were out-of-pocket expenses and 13% ($28,225,.801) were indirect costs. Thirty-three percent ($45,652,677/$137,204,393) of the total cost in children aged < 5 years was in the < 3-month age group, of which 52% ($71,654,002/$137,204,393) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3,307,218 in the < 3-month age group to $8,603,377 in the 9–11-month age group.ConclusionsAmong children < 5 years of age with RSV in South Africa, the highest cost burden was in the youngest infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness.

Factors Associated With Coronavirus Disease 2019 Vaccine Uptake Among Pregnant Women and Nonpregnant Women of Reproductive Age in Jamaica.

Despite high rates of coronavirus disease 2019 (COVID-19)-related maternal mortality, Jamaica currently has little data on COVID-19 vaccine uptake among pregnant women. We conducted a cross-sectional, web-based survey of 192 reproductive-aged women in Jamaica from February 1 to 8, 2022. Participants were recruited from a convenience sample of patients, providers, and staff at a teaching hospital. We assessed self-reported COVID-19 vaccination status and COVID-19-related medical mistrust (operationalized as vaccine confidence, government mistrust, and race-based mistrust). We used multivariable modified Poisson regression to test the association between vaccine uptake and pregnancy. Of 192 respondents, 72 (38%) were pregnant. Most (93%) were Black. Vaccine uptake was 35% in pregnant women versus 75% in nonpregnant women. Pregnant women were more likely to cite healthcare providers versus the government as trustworthy sources of COVID-19 vaccine information (65% vs 28%). Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination (adjusted prevalence ratio [aPR] = 0.68 [95% confidence interval {CI}, .49-.95], aPR = 0.61 [95% CI, .40-.95], and aPR = 0.68 [95% CI, .52-.89], respectively). Race-based mistrust was not associated with COVID-19 vaccination in the final model. Pregnancy, low vaccine confidence, and government mistrust were associated with a lower likelihood of COVID-19 vaccination among reproductive-aged women in Jamaica. Future studies should evaluate the efficacy of strategies proven to improve maternal vaccination coverage, including standing "opt-out" vaccination orders and collaborative provider and patient-led educational videos tailored for pregnant individuals. Strategies that decouple vaccine messaging from government agencies also warrant evaluation.