Research Kirsten Maertens

Abstract

Two vaccines designed for pregnant women, to protect their unborn infant, are entering late phase development and will prevent infections from group B Streptococcus and respiratory syncytial virus, respectively. For these vaccines to be approved, the vaccine must work effectively without causing any unwanted responses. To implement these vaccines in countries with low resources, healthcare systems must be strengthened by improving vaccine safety monitoring and surveillance of infection, and advancing vaccine delivery, vaccine confidence, and patient participation. The rapid rollout of electronic health records (EHR) in Kenya, Mozambique, Malawi, and Uganda offers an opportunity to use routine data to strengthen reporting of rates of adverse pregnancy, neonatal and infant outcomes, and any adverse events following immunisation; this will be imperative in informing and preparing for future large scale vaccination rollout campaigns. Our approach will address key gaps in EHR to develop pregnancy registries embedded within national reporting systems to establish this data, including baseline rates of pregnancy and infancy outcomes for Tetanus and COVID19 vaccines currently in use. These reporting systems will allow monitoring of potential safety signals once new vaccines are introduced. Experts in EHR, obstetrics and gynaecology, paediatrics, microbiology, clinical trials, and implementation research will develop the motivation and tools needed to monitor and evaluate current and future maternal vaccines. We will work closely with the WHO, African Medicines Agency and Country Stakeholders, co-developing pregnancy registries, sentinel site microbiological surveillance systems, and maternal vaccination communications toolkits in preparation for the decade of maternal vaccines. Our programme of work culminates in a network of maternal vaccine trial sites who can rapidly evaluate vaccines in pregnancy from late-stage trials through to introduction on a national level.

Researcher(s)

• Promoter: Maertens Kirsten
• Co-promoter: Hendrickx Greet

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Several RSV vaccine candidates, usually based on a recombinant form of the fusion (F) protein that is locked in the prefusion state, are in advanced stage of clinical development. These vaccines target the elderly and pregnant women despite the fact that the need may be greatest in children. It seems that for RSV, the prefusion F protein does not result in sufficient protective RSV immunity in children and adults, and that a correlate of protection (CoP) in children might be different than in adults. Determining a CoP for children turns out to be very challenging and many inconsistent results have been found. In this project, a comprehensive study will be done to map the antibody repertoire of pregnant women, newborns and young children up to 16 months, a.o. using an extensive panel of RSV F specific monoclonal antibodies. Subsequently, differences in the processing of the RSV F protein in primary epithelial cells of children and adults will be investigated by characterizing the virus in WD-PNECs, focusing on the structure of the F protein and the presence of different epitopes. Antibody repertoires and virus characteristics will be correlated with the onset and severity of RSV infection in children. Finally, monoclonal antibodies will be developed using subtractive immunization to target epitopes that correlate with a protective CoP in children. This will support the ultimate goal to find a CoP in children and will help to accelerate vaccine development in children.

Researcher(s)

• Promoter: Delputte Peter
• Co-promoter: Maertens Kirsten
• Fellow: Schaerlaekens Sofie

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

Pertussis is a contagious respiratory disease that mainly affects children under one year of age. Vaccines are available and can be administered from six weeks of age onwards, leaving infants unprotected in the first weeks of life. To close the susceptibility gap, vaccination in pregnancy has been implemented to enhance antibodies to cross the placenta towards the unborn child. However, also cell-mediated immune responses play an important role in clearing infections in the absence of antibodies, though research is lacking. The present study aims to investigate mother-to-child cytokine transport across the placenta after pertussis vaccination in pregnancy. Cytokine levels will be measured with the Meso Scale Discovery technology in maternal and cord blood samples at delivery from mother-infant pairs enrolled in a prior Belgian cohort study. This study will give deeper understanding of the immunobiology of maternal immunization and will further improve maternal/infant health.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Due to the high susceptibility and vulnerability of pregnant women, foetuses and infants to infectious diseases, maternal immunization has gained interest. Nevertheless, the optimal timepoint for vaccination in pregnancy is still unknown. Also, dynamic changes in immune function occur during pregnancy if a vaccine is given at a different gestational age. This may affect vaccine response and kinetics of vaccine-induced antibodies in blood and breastmilk in pregnant and lactating women. Additionally, since several recommendations for vaccination in pregnancy and in the postpartum period are currently in place, the question arises whether the administration of different vaccines has an impact on the immune responses to these vaccines and possibly causes an interaction in the kinetics of antibodies induced by these vaccines. Within this project, we aim to determine the optimal time point for vaccination in pregnancy, compare antibody kinetics and investigate potential interactions in immune responses when administering different vaccines (e.g. pertussis, COVID-19) in pregnancy or in the postpartum. We develop conceptual frameworks in which we combine statistical approaches with mathematical models of infectious diseases to improve the analysis and the design of maternal immunization studies. The focus of the project is on pertussis and COVID-19, but outcomes can be applied to infectious diseases for which vaccines can be administered in pregnancy or in the postpartum period.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

In view of its effectiveness to protect infants against several infectious diseases from immediately after birth, maternal immunization has gained interest in the last years. Yet, the optimal development of this vaccination strategy is still limited by the relatively poor understanding of the immunobiology of vaccine responses in pregnancy. Dynamic changes in immune function occur throughout the gestation which can impact vaccine responses in pregnant women when vaccinating at a different gestational age in pregnancy. Within this proposal, the effect of a different timing of vaccination in pregnancy on the cellular and on different aspects of the antibody-dependent immunity (titers, subclass, functionality, glycosylation) in blood will be studied. Also, the influence of this timing on the molecular basis of maternal antibody transfer across the placenta will be investigated. Additionally, a proof of concept investigating the impact of maternal vaccination and timing of maternal vaccination on breastmilk will be constructed. Within this proof of concept, quantitative and qualitative characteristics of breastmilk antibodies will be measured and an in-vitro M-cell model to measure the role of breastmilk in protecting infants from disease will be validated. Within this project, we will focus on pertussis as an example, but outcomes of this project can be applied to other infectious diseases for which vaccines can be administered in pregnancy like GBS, RSV, CMV, SARS-CoV-2…

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Pertussis (better known as whooping cough) is a vaccine-preventable respiratory tract infection mostly affecting infants who are too young to be protected by the currently available vaccines. To better protect these infants, pertussis vaccination during pregnancy has been introduced in a lot of countries worldwide. Vaccination with a tetanus, diphtheria, acellular pertussis vaccine raises the titer of disease-specific maternal antibodies in pregnant women which are then transferred to the newborn through transplacental transport and breastfeeding thereby providing passive protection to the infant in the first vulnerable weeks of life. Little evidence suggests that the antibodies ingested by the newborn via breastmilk provide local mucosal immunity in the enteric and respiratory tract, but whether they can actually be transported across the infant gut barrier into the circulation of the newborn possibly providing systemic protection is currently unexplored. The proposed project aims to develop and validate an in vitro microfold (M) cell model that mimics the infant gut barrier, to investigate the transport of secretory IgA (sIgA) antibodies in breastmilk from the enteric and respiratory tract into the systemic circulation. For this purpose, Caco-2 cells and Raji cells will be co-cultured on a transwell to form M cells, and the formation of M cells will be investigated with confocal microscopy. To validate the model, total sIgA antibodies in a limited number of breastmilk samples will be measured using ELISA before and after diffusion through the model. Once validated, total and pertussis-specific sIgA antibodies in breastmilk samples will be measured on a larger scale to determine the mucosal transport of antibodies across the infant gastrointestinal and respiratory tract . This model could be an effective and low-cost tool that contributes to exploring the impact of vaccination during pregnancy on protection provided by lactation. The project might also be the basis of more research within this field in the context of other immunoglobulins of importance and other infectious diseases for which vaccines can be administered during pregnancy.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Since pregnant women, fetuses and neonates are highly vulnerable to infectious diseases related morbidity and mortality, it of utmost important to understand barriers in the uptake of maternal vaccines to decrease vaccine hesitancy and increase vaccination coverage in fertile, pregnant and lactating women. Therefore a multidisciplinary team of experts at the University Antwerp is created, to investigate the different aspects of social media communication and its impact on vaccine confidence, acceptance and coverage in fertile, pregnant and lactating women. To study this, five research objectives are formulated: - Study the impact of the COVID-19 pandemic and increased social media communication and search behavior on attitude toward and confidence in maternal vaccines. - Develop a social listening and monitoring tool, specifically for maternal vaccination, that contributes to the systems map with social media data by identifying influential factors and that can monitor trends in vaccine hesitancy over time. - Identify interlinkage between influencing factors by using systemic thinking which may detect the dynamics among the factors that may lead to increase in vaccine confidence. - Experimental evaluation of the impact of potential social media communication strategies on behavior towards maternal vaccination. - Comparison of influential factors in different countries.

Researcher(s)

• Promoter: Maertens Kirsten
• Co-promoter: Daelemans Walter
• Co-promoter: Jacoby Alexis
• Co-promoter: Poels Karolien

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Women often want or need to be vaccinated during pregnancy or lactation. This may be with perspectives of a trip, booster vaccination or prevailing epidemics. Furthermore, vaccination during pregnancy is regarded as a valid method to provide immunological protection to the newborn. The systematic exclusion of pregnant and breastfeeding women from clinical vaccine studies means however that it often takes a long time before sufficient data are available on the effectiveness and safety of vaccination during these periods. This lack of data forces them to make uninformed risk-benefit decisions about their own health and the one of their newborn. In this prospective, multicohort, observational study, we aim to evaluate the safety and immunogenicity of COVID19-vaccination during pregnancy and lactation. Participants can freely choose to be vaccinated when they are invited through the governmental invitation scheme. Both mRNA vaccines and adenovector vaccines are accepted. To evaluate the immune response after vaccination against COVID-19, samples (blood, breastmilk, nasopharyngeal swabs) are taken at different timepoints before and after COVID-19 vaccination.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

The current coronavirus pandemic affects us all. As with all infections, certain subpopulations are more vulnerable to severe disease and even death and require therefore more research. In this pandemic, the elderly and immunologically fragile people are more prone to severe disease. Pregnant women and very young infants are traditionally also considered as immunologically different from the general population, certainly in view of infectious diseases. Since little to nothing is known to the scientific world of this new virus, researchers and health care personnel dealing with pregnant women and their neonates do have concerns on the risk they run. This project offers a unique opportunity to map the impact of the current pandemic in a vulnerable subpopulation of the society. The main objective of the project is to quantify the impact of the SARSCoV- 2 pandemic in pregnant women and their newborns/infants by assessing the rate of transmission, the overall health, mental well-being, immunological responses and clinical outcomes of clinicallysuspected and laboratory-confirmed COVID-19 infections in pregnant women and their neonates. Data will be collected through online questionnaires that will be send to pregnant women at a 2 week interval until 8 weeks postpartum. This will enables us to monitor possible COVID-19 infections in pregnancy and to look at possible adverse outcomes in pregnant women, fetuses and neonates. At 12 months postpartum, women will be contacted again to look at possible long-term consequences of COVID-19 infections in pregnancy on infants. Additionally, pregnant women participating in the surveillance study will be asked to provide maternal and cord blood samples at delivery to measure the prevalence of SARS-CoV-2 specific antibodies in pregnant women and newborns and to measure the transplacental transfer of SARS-CoV-2 specific antibodies from mother to infant during pregnancy. Data from this project will be used to formulate evidence-based recommendations on prevention, treatment and vaccination for COVID-19 in pregnant women and neonates. Additionally, this project will provide information for policy makers and experts in the field on public health measures and management of pregnant women and neonates during this pandemic.

Researcher(s)

• Promoter: Maertens Kirsten
• Co-promoter: Leuridan Elke
• Co-promoter: Van Damme Pierre

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

The current coronavirus pandemic affects us all. As with all infections, certain subpopulations are more vulnerable to severe disease and even death and require therefore more research. In this pandemic, the elderly and immunologically fragile people are more prone to severe disease. Pregnant women and very young infants are traditionally also considered as immunologically different from the general population, certainly in view of infectious diseases. Since little to nothing is known to the scientific world of this new virus, researchers and health care personnel dealing with pregnant women and their neonates do have concerns on the risk they run. This project offers a unique opportunity to map the impact of the current pandemic in a vulnerable subpopulation of the society. The main objective of the project is to quantify the impact of the SARSCoV- 2 pandemic in pregnant women and their newborns/infants by assessing the rate of transmission, the overall health, mental well-being, immunological responses and clinical outcomes of clinicallysuspected and laboratory-confirmed COVID-19 infections in pregnant women and their neonates. Data will be collected through online questionnaires that will be send to pregnant women at a 2 week interval until 8 weeks postpartum. This will enables us to monitor possible COVID-19 infections in pregnancy and to look at possible adverse outcomes in pregnant women, fetuses and neonates. At 12 months postpartum, women will be contacted again to look at possible long-term consequences of COVID-19 infections in pregnancy on infants. Additionally, pregnant women participating in the surveillance study will be asked to provide maternal and cord blood samples at delivery to measure the prevalence of SARS-CoV-2 specific antibodies in pregnant women and newborns and to measure the transplacental transfer of SARS-CoV-2 specific antibodies from mother to infant during pregnancy. Data from this project will be used to formulate evidence-based recommendations on prevention, treatment and vaccination for COVID-19 in pregnant women and neonates. Additionally, this project will provide information for policy makers and experts in the field on public health measures and management of pregnant women and neonates during this pandemic.

Researcher(s)

• Promoter: Van Damme Pierre
• Co-promoter: Leuridan Elke
• Co-promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

No abstract is available in English since this project is conducted on behalf of "Vlaams Agentschap Zorg en Gezondheid" and measures the vaccination coverage in toddlers, adolescents, pregnant women, health care workers in Flanders, Belgium.

Researcher(s)

• Promoter: Maertens Kirsten
• Co-promoter: Van Damme Pierre

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Despite successful universal pertussis vaccination programs, the disease remains an important public health problem and is nowadays still one of the most common vaccine-preventable diseases in the world. The highest incidence and disease burden can be found in infants below one year of age, too young to be completely protected by the available vaccines and vaccinations schedules. To better protect these infants, maternal pertussis vaccination has been introduced in a number of countries, including Belgium. Scientific evidence on several aspects of this vaccination strategy has boomed over the last years. However, some aspects of this vaccination strategy such as the long-term effect of the strategy on the infant's immune system and the recommended time frame between repeat booster Tdap vaccinations in successive pregnancies have never been investigated. To fill these knowledge gaps, we will look at the humoral immune response in children from mothers vaccinated with Tdap during pregnancy compared to children from unvaccinated mothers before and after a booster dose with a tetravalent aP containing vaccine in the first year of primary school. Also, we will look at antibody concentrations in mothers at delivery and cord blood upon a subsequent delivery. Results from these laboratory tests will feed a mathematical model to describe kinetics of antibodies in children in the presence and absence of maternal antibodies and will help us to make a recommendation on the recommended time frame between repeat booster Tdap vaccinations to have sufficient maternal antibodies at a next delivery. The present proposal will enable fine-tuning of the maternal vaccinations recommendations and existing booster policies in children after maternal vaccination.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Despite successful universal pertussis vaccination programs, the disease remains an important public health problem and is still one of the most common vaccine-preventable diseases in the world. The highest incidence and disease burden can be found in infants below one year, too young to be completely protected by the available vaccines and vaccination schedules. To protect these infants, alternative vaccination strategies are needed. During recent years, maternal pertussis vaccination has been introduced in a number of countries. Scientific evidence on several aspects of this strategy has boomed over the last years. While interference of maternal pertussis immunization was shown on the infant's immune response after priming and first booster dose in the second year of life, knowledge on several other aspects, such as the long-term effects of the strategy on the immune responses of children later in life, is lacking. Therefore, we will look at both humoral and cellular immune responses and functionality of antibodies before and after a second booster dose of a tetravalent aP containing vaccine in children from mothers vaccinated with a Tdap vaccine during pregnancy compared to children from unvaccinated mothers. Results from these laboratory tests will feed a mathematical model to describe kinetics of antibodies in the presence or abscense of maternal antibodies in those children. The present proposal will enable fine-tuning of existing booster policies after maternal vaccination.

Researcher(s)

• Promoter: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project

Abstract

Despite the availability of successful universal pertussis vaccination programs, the disease remains an important global public health problem and is nowadays one of the most common vaccinepreventable diseases in the world. The highest incidence and disease burden can be found in infants below one year of age, too young to be completely protected by the currently available vaccines and vaccination schedules. To protect these vulnerable infants, alternative vaccination strategies, such as maternal vaccination, are needed. During the last years, maternal pertussis vaccination has been introduced in an increasing number of countries. Scientific evidence on different effects of this vaccination strategy has boomed during the last years. However, knowledge on several important aspects of this strategy is still lacking. Therefore, the overall aim of this research proposal is to unravel the basic principles behind the maternal (pertussis) vaccination strategy. To achieve this, eight different aims are formulated in this research proposal each looking at a different immunological aspect of the vaccination strategy. We are convinced that the results of this research proposal will not only be supportive for the current recommendation on maternal pertussis vaccination, but will also help to understand the immunological mechanisms that will be used in new vaccines that are currently under development and have the potential to be used in pregnant women like GBS, RSV, CMV, Zika….

Researcher(s)

• Promoter: Van Damme Pierre
• Fellow: Maertens Kirsten

Research team(s)

• Centre for the Evaluation of Vaccination (CEV)

Project type(s)

• Research Project