Maternal Vaccination to Prevent Adverse Pregnancy Outcomes: An Underutilized Molecular Immunological Intervention?

[Display omitted] •Include pregnant people: It can no longer be accepted to a priori exclude pregnant people from vaccine studies.100,101•Emphasize data collection in LMIC: studies conducted in LMIC and lead by LMIC investigators on birth outcomes in relation to maternal vaccination are urgently needed.•Priority Shift: It is unacceptable that funding focused on adverse pregnancy outcomes represents the lowest investment along the continuum of care (1, 104). Adverse pregnancy outcomes including maternal mortality, stillbirth, preterm birth, intrauterine growth restriction cause millions of deaths each year. More effective interventions are urgently needed. Maternal immunization could be one such intervention protecting the mother and newborn from infection through its pathogen-specific effects. However, many adverse pregnancy outcomes are not directly linked to the infectious pathogens targeted by existing maternal vaccines but rather are linked to pathological inflammation unfolding during pregnancy. The underlying pathogenesis driving such unfavourable outcomes have only partially been elucidated but appear to relate to altered immune regulation by innate as well as adaptive immune responses, ultimately leading to aberrant maternal immune activation. Maternal immunization, like all immunization, impacts the immune system beyond pathogen-specific immunity. This raises the possibility that maternal vaccination could potentially be utilised as a pathogen-agnostic immune modulatory intervention to redirect abnormal immune trajectories towards a more favourable phenotype providing pregnancy protection. In this review we describe the epidemiological evidence surrounding this hypothesis, along with the mechanistic plausibility and present a possible path forward to accelerate addressing the urgent need of adverse pregnancy outcomes.