Background

Reducing neonatal and thus under-five mortality and morbidity is a millennium development goal. Immunization in pregnancy is a promising approach to achieving this goal. It prevents infectious diseases and their complications by direct protection of the mothers as well as by indirect protection of the neonate by intrauterine antibody transfer from mother to child. Vaccines are available to prevent tetanus, influenza and pertussis during pregnancy and early life. They are now being systematically evaluated and increasingly recommended for global introduction as part of a immunization in pregnancy platform. Promising vaccines are in development for global use and include group B streptococcal (GBS) and respiratory syncytial virus (RSV) vaccines.

Introduction of these vaccines comes with tremendous potential benefit specifically for low and middle income countries (LMIC). However, there is much at stake when it comes to immunization of pregnant women. The safety of any product given to these primarily healthy pregnant women and their unborn babies is under specific professional and public scrutiny. Safety concerns related to immunization in pregnancy are unlikely to affect pregnancy immunization programs alone, particularly when the vaccines are also used in routine childhood and adult immunization programs, such as influenza and pertussis vaccines. Therefore, product or program specific safety issues need to be identified to appropriately assess the benefit-risk profile of these vaccines and their implementation programs and to protect the target population from unintended harm. On the other hand, unfounded public or professional concerns can jeopardize beneficial vaccine programs and need to be rapidly refuted based on rigorous science and globally well-coordinated decision making and communication.

The GAIA project was initiated for an initial period of 32 months in response to the call of the World Health Organization (WHO) for a globally harmonized approach to actively monitor the safety of vaccines and immunization in pregnancy programs with a specific focus on LMICs needs and requirements. Additionally, a WHO consultation identified later on the currently fragmented research, the current lack of data comparability as well as the need to improve the quality of safety data to inform decision-making and system strengthening. In that 32-month PHASE I of the GAIA project, experts from 13 organizations have collaborated with over 500 volunteers worldwide from all continents.

The WHO Global Advisory Committee on Vaccine Safety (GACVS) provided a highly supportive assessment and recommends the use of the key GAIA guidance document which refers to and aligns all other GAIA standards and tools developed for use in clinical trials. WHO officially recommends the use of Brighton Case definitions in the Global Manual on Surveillance of AEFI as well as in their AEFI country trainings for LMIC.

Furthermore, an informal working group of regulatory agencies, including professionals from the FDA, the EMA and Health Canada, was formed in recognition of the need for enhanced global interaction and this group sees value and is currently exploring options and requirements for consideration of GAIA standards for regulatory purposes. An informal working group of vaccine manufacturers has also emphasized the usefulness of GAIA case definitions, has reported immediate use of GAIA standards in clinical trials and observational studies, and is keen for the platform to develop pre-competitive standards of use for all manufacturers.

However, great efforts are still to be done in the field in order to ensure wider applicability, usefulness and acceptability of the tools and standards developed, especially in LMIC.