Quantitative analysis of pertussis, tetanus, and diphtheria antibodies in sera and breast milk from Tdap vaccinated women using a qualified multiplex assay.

Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Immunization with Multiple Virulence Factors Provides Maternal and Neonatal Protection against Group B Streptococcus Serotypes.

Group B streptococcus (GBS) commonly colonizes the vaginal tract and is a leading cause of life-threatening neonatal infections and adverse pregnancy outcomes. No effective vaccine is clinically available. Conserved bacterial virulence factors, including those of GBS, have been employed as vaccine components. We investigated serotype-independent protection against GBS by intranasal immunization with six conserved GBS virulence factors (GBSV6). GBSV6 induced systemic and vaginal antibodies and T cell responses in mice. The immunity reduced mouse mortality and vaginal colonization by various GBS serotypes and protected newborn mice of immunized dams against GBS challenge. Intranasal GBSV6 immunization also provided long-lasting protective immunity and had advantages over intramuscular GBSV6 immunization regarding restricting vaginal GBS colonization. Our findings indicate that intranasal immunization targeting multiple conserved GBS virulence factors induces serotype-independent immunity, which protects against GBS infection systemically and vaginally in dams and prevents newborn death. The study presents valuable strategies for GBS vaccine development.

"Maternal Vaccination Greatly Depends on Your Trust in the Healthcare System": A Qualitative Study on the Acceptability of Maternal Vaccines among Pregnant Women and Healthcare Workers in Barcelona, Spain.

The World Health Organization (WHO) identified vaccine hesitancy as one of the top 10 threats to global health in 2019. Health promotion and education have been seen to improve knowledge and uptake of vaccinations in pregnancy. This qualitative study was conducted based on phenomenology, a methodological approach to understand first-hand experiences, and grounded theory, an inductive approach to analyse data, where theoretical generalisations emerge. Data were collected through semi-structured interviews with pregnant women attending antenatal care services and healthcare workers (HCWs) in Barcelona, Spain. Interviews were audio-recorded, transcribed, and coded, and notes were taken. Inductive thematic analysis was performed, and data were manually coded. Pertussis was reported as the most trusted vaccine among pregnant women due to its long-standing background as a recommended vaccine in pregnancy. The influenza vaccine was regarded as less important since it was perceived to cause mild disease. The COVID-19 vaccine was the least trustworthy for pregnant women due to uncertainties about effectiveness, health effects in the mid- and long-term, the fast development of the vaccine mRNA technology, and the perceptions of limited data on vaccine safety. However, the necessity to be vaccinated was justified by pregnant women due to the exceptional circumstances of the COVID-19 pandemic. The recommendations provided by HCW and the established relationship between the HCW, particularly midwives, and pregnant women were the main factors affecting decision-making. The role of mass media was perceived as key to helping provide reliable messages about the need for vaccines during pregnancy. Overall, vaccines administered during pregnancy were perceived as great tools associated with better health and improved quality of life. Pregnancy was envisioned as a vulnerable period in women's lives that required risk-benefits assessments for decision-making about maternal vaccinations. A holistic approach involving the community and society was considered crucial for health education regarding maternal vaccines in support of the work conducted by HCWs.

Women's views and experiences of accessing pertussis vaccination in pregnancy and infant vaccinations during the COVID-19 pandemic: A multi-methods study in the UK.

BACKGROUND: COVID-19 changed access to healthcare, including vaccinations, in the United Kingdom (UK). This study explored UK women's experiences of accessing pertussis vaccination during pregnancy and infant vaccinations during COVID-19. METHODS: An online cross-sectional survey was completed, between 3rd August-11th October 2020, by 1404 women aged 16+ years who were pregnant at some point after the first UK lockdown from March 23rd, 2020. Ten follow-up semi-structured interviews were conducted. RESULTS: Most women surveyed were pregnant (65.7%) and a third postnatal (34.3%). Almost all women (95.6%) were aware that pertussis vaccination is recommended in pregnancy. Most pregnant (72.1%) and postnatal women (84.0%) had received pertussis vaccination; however, access issues were reported. Over a third (39.6%) of women had a pregnancy vaccination appointment changed. COVID-19 made it physically difficult to access pregnancy vaccinations for one fifth (21.5%) of women and physically difficult to access infant vaccinations for almost half of women (45.8%). Nearly half of women (45.2%) reported feeling less safe attending pregnancy vaccinations and over three quarters (76.3%) less safe attending infant vaccinations due to COVID-19. The majority (94.2%) felt it was important to get their baby vaccinated during COVID-19. Pregnant women from ethnic-minorities and lower-income households were less likely to have been vaccinated. Minority-ethnicity women were more likely to report access problems and feeling less safe attending vaccinations for both themselves and their babies. Qualitative analysis found women experienced difficulties accessing antenatal care and relied on knowledge from previous pregnancies to access vaccines in pregnancy. CONCLUSION: During the ongoing and future pandemics, healthcare services should prioritise equitable access to routine vaccinations, including tailoring services for ethnic-minority families who experience greater barriers to vaccination.

Every Country, Every Family: Time to Act for Group B Streptococcal Disease Worldwide.

The global burden of Group B Streptococcus (GBS) was estimated for 2015 prompting inclusion of GBS as a priority in the Global Meningitis Roadmap. New estimates for the year 2020 and a WHO report analysing the full value of GBS maternal vaccines has been launched to advance evidence based decision making for multiple stakeholders. In this first of a 10-article supplement, we discuss the following (1) gaps in evidence and action, (2) new evidence in this supplement, and (3) what actions can be taken now and key research gaps ahead. We call for investment in the research pipeline, notably description, development, and delivery, in order to accelerate progress and address the large burden of GBS for every family in every country.

Maternal Vaccination in Uganda: Exploring Pregnant Women, Community Leaders and Healthcare Workers' Perceptions.

Background: We investigated pregnant women, community leaders, healthcare workers (HCWs) and programme managers' perceptions of maternal vaccination in Kampala, Uganda. Methods: We conducted focus group discussions, key informant interviews and in-depth discussions with HCWs (3), community leaders (3), pregnant women (8) and programme managers (10) between November 2019 and October 2020. Data were analysed thematically. Results: Pregnant women, community leaders and some HCWs had limited maternal immunisation knowledge. There was confusion over what constitutes a vaccine. Pregnant women may not receive vaccines because of mistrust of government; use of expired vaccines; reliance on traditional medicine; religious beliefs; fear of side effects; HCWs attitudes; and logistical issues. The key facilitators of maternal vaccination were a desire to prevent diseases, positive influences from HCWs and information about vaccine side effects. Community leaders and some pregnant women highlighted that pregnant women do not make decisions about maternal vaccination independently and are influenced by different individuals, including other pregnant women, older people, partners, relatives (parents), community leaders, HCWs and the government. Conclusions: Our results indicate that public health messaging should target all community members, including partners and parents of pregnant women as well as HCWs, to improve knowledge of and confidence in maternal vaccines.

Decision-making process for introduction of maternal vaccines in Kenya, 2017-2018.

BACKGROUND: Maternal immunization is a key strategy for reducing morbidity and mortality associated with infectious diseases in mothers and their newborns. Recent developments in the science and safety of maternal vaccinations have made possible development of new maternal vaccines ready for introduction in low- and middle-income countries. Decisions at the policy level remain the entry point for maternal immunization programs. We describe the policy and decision-making process in Kenya for the introduction of new vaccines, with particular emphasis on maternal vaccines, and identify opportunities to improve vaccine policy formulation and implementation process. METHODS: We conducted 29 formal interviews with government officials and policy makers, including high-level officials at the Kenya National Immunization Technical Advisory Group, and Ministry of Health officials at national and county levels. All interviews were recorded and transcribed. We analyzed the qualitative data using NVivo 11.0 software. RESULTS: All key informants understood the vaccine policy formulation and implementation processes, although national officials appeared more informed compared to county officials. County officials reported feeling left out of policy development. The recent health system decentralization had both positive and negative impacts on the policy process; however, the negative impacts outweighed the positive impacts. Other factors outside vaccine policy environment such as rumours, sociocultural practices, and anti-vaccine campaigns influenced the policy development and implementation process. CONCLUSIONS: Public policy development process is complex and multifaceted by its nature. As Kenya prepares for introduction of other maternal vaccines, it is important that the identified policy gaps and challenges are addressed.

Adverse Outcomes in Pregnant Women Hospitalized With Respiratory Syncytial Virus Infection: A Case Series.

We identified 10 women hospitalized with respiratory syncytial virus infection during pregnancy. Diagnoses included pneumonia/atelectasis (5), respiratory failure (2), and sepsis (2). Six had obstetrical complications during hospitalization, including 1 induced preterm birth. One required intensive care unit admission and mechanical ventilation. Four infants had complications at birth.

"Vaccines for pregnant women ?! Absurd" - Mapping maternal vaccination discourse and stance on social media over six months.

OBJECTIVE: To understand the predominant topics of discussion, stance and associated language used on social media platforms relating to maternal vaccines in 15 countries over a six-month period. BACKGROUND: In 2019, the World Health Organisation prioritised vaccine hesitancy as a top ten global health threat and recognized the role of viral misinformation on social media as propagating vaccine hesitancy. Maternal vaccination offers the potential to improve maternal and child health, and to reduce the risk of severe morbidity and mortality in pregnancy. Understanding the topics of discussion, stance and language used around maternal vaccines on social media can inform public health bodies on how to combat vaccine misinformation and vaccine hesitancy. METHODS: Social media data was extracted (Twitter, forums, blogs and comments) for six months from 15 countries (Australia, Brazil, Canada, France, Germany, India, Italy, Korea, Mexico, Panama, South Africa, Spain, United Kingdom and United States). We used stance, discourse and topic analysis to provide insight into the most frequent and weighted keywords, hashtags and themes of conversation within and across countries. RESULTS: We exported a total of 19,192 social media posts in 16 languages obtained between 1st November 2018 and 30th April 2019. After screening all posts, 16,000 were included in analyses, while excluding retweets, 2,722 were annotated for sentiment. Main topics of discussion were the safety of the maternal influenza and pertussis vaccines. Discouraging posts were most common in Italy (44.9%), and the USA (30.8%). CONCLUSION: The content and stance of maternal vaccination posts from November 2018 to April 2019 differed across countries, however specific topics of discussion were not limited to geographical location. These discussions included the promotion of vaccination, involvement of pregnant women in vaccine research, and the trust and transparency of institutions. Future research should examine the relationship between stance (promotional, neutral, ambiguous, discouraging) online and maternal vaccination uptake in the respective regions.

A Vaccine Against Group B Streptococcus: Recent Advances.

Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide - protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.

Maternal and neonatal data collection systems in low- and middle-income countries: scoping review protocol.

Background: Pregnant women and neonates represent one of the most vulnerable groups, especially in low- and middle-income countries (LMICs). A recent analysis reported that most vaccine pharmacovigilance systems in LMICs consist of spontaneous (passive) adverse event reporting. Thus, LMICs need effective active surveillance approaches, such as pregnancy registries. We intend to identify currently active maternal and neonatal data collection systems in LMICs, with the potential to inform active safety electronic surveillance for novel vaccines using standardized definitions. Methods: A scoping review will be conducted based on established methodology. Multiple databases of indexed and grey literature will be searched with a specific focus on existing electronic and paper-electronic systems in LMICs that collect continuous, prospective, and individual-level data from antenatal care, delivery, neonatal care (up to 28 days), and postpartum (up to 42 days) at the facility and community level, at the national and district level, and at large hospitals. Also, experts will be contacted to identify unpublished information on relevant data collection systems. General and specific descriptions of Health Information Systems (HIS) extracted from the different sources will be combined and duplicated HIS will be removed, producing a list of unique statements. We will present a final list of Maternal, Newborn, and Child Health systems considered flexible enough to be updated with necessary improvements to detect, assess and respond to safety concerns during the introduction of vaccines and other maternal health interventions. Selected experts will participate in an in-person consultation meeting to select up to three systems to be further explored in situ. Results and knowledge gaps will be synthesized after expert consultation.

Beyond the verbal: Pregnant women's preferences for receiving influenza and Tdap vaccine information from their obstetric care providers.

OBJECTIVE: Prenatal providers are pregnant women's most trusted sources of health information, and a provider's recommendation is a strong predictor of maternal vaccine receipt. However, other ways women prefer receiving vaccine-related information from prenatal providers, aside from face-to-face conversations, is unclear. This study explores what secondary communication methods are preferred for receiving maternal vaccine-related information. STUDY DESIGN: Obstetric patients at four prenatal clinics around Atlanta, Georgia received a 27-item survey between May 5th, 2016 and June 15th, 2016. Participants were asked about sources they currently use to obtain prenatal health information and their preferences for receiving vaccine-related information from providers. Descriptive statistics were calculated and chi-square tests were used to evaluate associations between participant characteristics and outcomes. RESULTS: Women primarily reported using the CDC website (57.7%) and pregnancy-related websites (53.0%) to obtain vaccine information. Apart from clinical conversations, educational brochures (64.9%) and e-mails (54.7%) were the preferred methods of receiving vaccine information from providers, followed by their provider's practice website (42.1%). Communication preferences and interest in maternal immunization varied by race/ethnicity, age and education; white women were twice as likely to want information on a provider's practice website compared to African-American women (OR = 2.06; 95% CI: 1.31, 3.25). CONCLUSIONS: Pregnant women use the Internet for information about vaccines, but they still value input from their providers. While e-mails and brochures were the preferred secondary modes of receiving information, a provider's existing practice website offers a potential communications medium that capitalizes on women's information seeking behaviors and preferences while limiting burden on providers.

The Role of Maternal HIV Envelope-Specific Antibodies and Mother-to-Child Transmission Risk.

Despite the wide availability of antiretroviral therapy (ART) prophylaxis during pregnancy, >150,000 infants become infected through mother-to-child transmission (MTCT) of HIV worldwide. It is likely that additional intervention strategies, such as a maternal HIV vaccine, will be required to eliminate pediatric HIV infections. A deeper understanding of the fine specificity and function of maternal HIV envelope (Env)-specific responses that provide partial protection against MTCT will be critical to inform the design of immunologic strategies to curb the pediatric HIV epidemic. Recent studies have underlined a role of maternal HIV Env-specific neutralizing and non-neutralizing responses in reducing risk of MTCT of HIV and in prolonging survival rates in HIV-infected infants. However, critical gaps in our knowledge include (A) the specific role of maternal autologous-virus IgG-neutralizing responses in driving the selection of infant transmitted founder (T/F) viruses and (B) Env mechanisms of escape from maternal autologous virus-neutralizing antibodies (NAbs). A more refined understanding of the fine specificities of maternal autologous virus NAbs and ways that maternal circulating viruses escape from these antibodies will be crucial to inform maternal vaccination strategies that can block MTCT to help achieve an HIV-free generation.

Maternal Immunization with Pneumococcal Polysaccharide Vaccine: Persistence of Maternal Antibodies in Infants.

OBJECTIVE: To evaluate the level and the persistence of maternal antibodies in infants after maternal immunization with pneumococcal polysaccharide vaccine (Pn23V). METHODS: Pregnant women were assigned to two groups, during routine low-risk pre-natal visits. The first Group (VAC) received the Pn23V vaccine shortly after enrolment at 28 weeks or later, and the second Group (NO_VAC) received no vaccine. To investigate the antibody persistence, we collected blood samples from the mothers after 1 month of delivery and from the infants at 1 and 6 months of age. RESULTS: Antibody titers were measured for serotypes 1, 6B and 14. Geometric mean antibody concentrations of specific immunoglobulin G were significantly higher in the vaccinated group compared with unvaccinated controls for all three serotypes tested. CONCLUSION: Despite the antibody level's decline, at 6 months of age, proportions >0.35 µg/ml remained higher in the infants of vaccinated mothers than controls for all three serotypes.