Mirjana Nesin

Immunogenicity and efficacy of influenza immunization during pregnancy: recent and ongoing studies

Pregnant women and young infants are at increased risk from influenza. The World Health Organization and public health guidelines from Australia, Canada, and the United States recommend immunizing pregnant women with trivalent inactivated influenza vaccine. However, there are multiple barriers to the uptake of this recommendation. Additionally, current vaccines are not licensed for infants <6 months of age. Immunizing pregnant women would provide protection to both mothers and infants. The Bill & Melinda Gates Foundation (BMGF) and the National Institute of Allergy and Infectious Diseases (NIAID) are trying to address some of the issues associated with maternal immunization, which could be an effective intervention in both high- and low-resource settings to combat the significant maternal and infant morbidity and mortality due to influenza. BMGF and NIAID efforts are complementary to each other, focusing on evaluating the immunogenicity, efficacy, and safety of influenza vaccines during pregnancy; and the potential effect of maternal immunization on outcomes in infants in low-resource populations.

Designing Drug Trials: Considerations for Pregnant Women

Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate.

Assessment of Safety in Newborns of Mothers Participating in Clinical Trials of Vaccines Administered During Pregnancy

A panel of experts convened by the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, developed proposed guidelines for the evaluation of adverse events in newborns of women participating in clinical trials of maternal immunization in the United States.

Small for gestational age: Case definition & guidelines for data collection, analysis, and presentation of maternal immunisation safety data

2017 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Assessment of Congenital Anomalies in Infants Born to Pregnant Women Enrolled in Clinical Trials

In 2011 and 2012, the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health, held a series of meetings to provide guidance to investigators regarding study design of clinical trials of vaccines and antimicrobial medications that enroll pregnant women. Assessment of congenital anomalies among infants born to women enrolled in these trials was recognized as a challenging issue, and a workgroup with expertise in epidemiology, pediatrics, genetics, dysmorphology, clinical trials, and infectious diseases was formed to address this issue. The workgroup considered 3 approaches for congenital anomalies assessment that have been developed for use in other studies: (1) maternal report combined with medical records review, (2) standardized photographic assessment and physical examination by a health professional who has received specific training in congenital anomalies, and (3) standardized physical examination by a trained dysmorphologist (combined with maternal interview and medical records review). The strengths and limitations of these approaches were discussed with regard to their use in clinical trials. None of the approaches was deemed appropriate for use in all clinical trials. Instead, the workgroup acknowledged that decisions regarding the optimal method of assessment of congenital anomalies will likely vary depending on the clinical trial, its setting, and the agent under study; in some cases, a combination of approaches may be appropriate. The workgroup recognized the need for more research on approaches to the assessment of congenital anomalies to better guide investigators in optimal design of clinical trials that enroll pregnant women.

Congenital microcephaly: Case definition & guidelines for data collection, analysis, and presentation of safety data after maternal immunisation

2017 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Maternal immunization efforts of the National Institutes of Health.

Over the last 35 years, efforts at the National Institutes of Health (NIH) to protect mothers and their infants against infectious diseases have involved a bench-to-bedside approach. Basic and translational research that provided a foundation for clinical trials of vaccines in pregnancy include natural history and vaccine antigen identification studies. Development of laboratory assays and reagents have been funded by NIAID; these are critical for the advancement of vaccine candidates through the preclinical and clinical steps along the maternal immunization research pathway to support vaccine efficacy. Animal models of maternal immunization have been developed to evaluate efficacy of vaccine candidates. Clinical studies required development of maternal immunization protocols to address specific pregnancy related issues, for enrollment and safety assessment of mothers and their infants. NIH has organized and participated in meetings, workshops and other collaborative efforts with partners have advanced maternal immunization efforts. Partners have included many institutes and offices at NIH as well as other Department of Health and Human Services agencies and offices (Food and Drug Administration, Centers for Disease Control and Prevention, National Vaccine Program Office), World Health Organization, academic investigators, Biotech and pharmaceutical companies, and nonprofit organizations such as the Bill and Melinda Gates Foundation. These research and development partnership are essential for advancing maternal immunization. Continued efforts are needed to promote maternal immunization to protect pregnant women and their infants against vaccine-preventable infectious disease, especially in resource-limited settings where the burden of infections is high.

Vaccine monitoring systems: A potential model for medications in pregnancy.

Multiple vaccine safety systems contribute to monitor and assess the safety of vaccines given to pregnant women and their offspring. This article presents a review of the strengths and limitations of several national vaccine safety systems. The review concludes that the present framework of vaccine safety systems offers lessons to be learned toward the design of a system for monitoring and assessing the safety of medications administered to pregnant women in clinical practice and research.

Maternal Immunization: Current status and future prospects.

Ajoke.sobanjo-termeulen@gatesfoundation.org Overwhelming evidence demonstrates the benefits of vaccines o individuals (both children and adults) and to the public, priarily via herd immunity. The Global Vaccine Action Plan (GVAP), pproved by the World Health Assembly in 2012, strives to ‘proide full benefits of vaccination to all people’, while Millennium evelopment Goals 4 and 5 work toward reduced child mortality nd improved maternal health. Immunizing mothers during pregancy (MI) against vaccine-preventable diseases has the potential o improve health outcomes in both mothers and their infants and o meet GVAP and Millennium Goals. MI may emerge as a key stratgy to address neonatal mortality in particular, which accounts for lmost half of all under five deaths globally. Aside from the success of the Maternal and Neonatal Tetanus limination (MNTE) program, population data are now available for ther successful MI programs, for example, in Argentina (described n this issue), and in the United Kingdom [1]. These programs have emonstrated the feasibility and effectiveness of MI programs in igh, medium and low income counties. No safety signals related to he vaccines administered as part of these programs were observed. An increasing amount of data regarding the efficacy and mmunogenicity of MI in both mothers and their infants are becomng available. For example, studies have demonstrated the efficacy f influenza vaccines in protecting pregnant women and their nfants, and the safety and effectiveness of maternal Tdap vacciation has been demonstrated in a large population of pregnant omen [1–3]. There is the potential for the results of ongoing trials f new RSV and GBS vaccines to contribute to the basis of licensure or a MI indication. An enabling regulatory and policy environment ould facilitate introduction of new, and expanding indications of icensed, vaccines to include pregnant women. However, major knowledge gaps and implementation chalenges remain. They are related to the lack of descriptive pidemiologic data, especially in low and medium income ountries (LMICs); the lack of harmonized definitions across tudies, allowing meta-analyses and improved pharmacovigilance cross studies and reporting systems; better understanding of nfrastructure and experience with conducting clinical trials in MICs settings; lack of integrated approaches to antenatal care, etc. he manuscripts included in this issue attempt to address some f these challenges: several studies describe the epidemiology of accine-preventable diseases (Polack et al., Halasa et al., Searle t al.); address harmonization of terms and definitions (Munoz t al.; Fulton et al.); provide perspective by researchers in LICs Laufer et al., Cutland et al.); and describe regulatory (Gruber) and thical (White and Madhi) aspects of MI. Strong partnerships among a diverse set of institutions and eographies are needed to overcome knowledge gaps, implement