London 12-13 February 2020

The workshop on maternal immunization against Emerging Infectious Diseases (EIDs) was held to review current evidence and generate initial guidance and next steps for CEPI-funded Lassa vaccine projects. The goal will be to ultimately enable the use of these novel EID vaccines in pregnant and lactating women.

Existing experience with maternal immunization, including in low-and-middle income countries (LMICs), holds lessons for future clinical trials against EIDs. Important conclusions from a recent WHO consultation, field experience from The Gambia, and practical case studies underlined the need for the timely consideration of preclinical and clinical data generation including trials in pregnant and lactating women.

A brief update on the current SARS-CoV-2 outbreak emphasized the importance of preparedness against Pathogen X and outlined regulatory considerations for clinical trials (CTs) in pregnant women. Lessons learned from the Ebola outbreak highlighted the challenges leading to the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) recommendation for the use of the vaccine in an emergency setting. The strong rationale to proactively include pregnant and lactating women in the development of vaccines against EIDs was further supported by a review of Lassa Fever epidemiology and the clinical evidence supporting a specific need to protect pregnant women from the increased morbidity and mortality due to Lassa infection.

Several critical enablers for the conduct of vaccine trials in pregnant and lactating women were identified. Experienced panellists provided testimony and practical guidance for the importance of ethical considerations, community engagement and the adequate communication of risks. Early engagement, clear communication and the continued care for the infants were considered as critical to the acceptance of clinical trials in pregnant women.
Breakout sessions provided an opportunity to benefit from the rich and diverse experience of participants with the aim to generate recommendations for next steps towards the inclusion of pregnant and lactating women in Lassa vaccine development.
The discussion of technical considerations concluded that Developmental & Reproductive Toxicology (DART) studies are a requirement and may be complemented by non- Good Laboratory Practices (GLP) preclinical studies to address specific questions. . The cumulative safety data from similar vaccine technology platforms targeting other pathogens can potentially be leveraged. But each Lassa vaccine candidate will need a careful and specific risk-benefit assessment, including a tailored preclinical and clinical development plan for evaluation in pregnant and lactating women.

Critical operational prerequisites for CTs in pregnant women include appropriate liability coverage and insurance, experienced staff and adequate capacity to perform pregnancy related assessments and provide care at and after delivery. Baseline epidemiology data should be available on disease burden as well as background pregnancy outcomes in the region.

No consensus could be reached on the minimum clinical data package needed before and optimal timing of CTs in pregnant women. A thorough benefit-risk assessment should guide CT design in pregnant women. There was agreement that vaccination from 2nd trimester makes sense to protect the mother and allow transfer of antibodies to the foetus. Safety surveillance of both the mother and the newborn/infant should be ensured and the immunological assessment of newborns could provide important input into the overall benefit-risk analysis for maternal immunization.

The concluding plenary confirmed the need to proactively include pregnant women in the development of vaccines against EIDs. While there are certain general considerations and requirements, it will be important to devise specific plans for each vaccine candidate. These concrete plans will be required for future discussions with regulatory agencies, who expressed a willingness to consider the specificities related to vaccines against EIDs.