Vaccine responses in newborns

Abstract

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life.

Pertussis (whooping cough)

“…In the UK and Australia, which have an accelerated primary vaccination schedule at 2, 3, and 4 months, higher incidence and hospitalisation rate is observed in those under 3 months old compared with older infants 7. Mortality is high in this group,189 possibly due to an immature immune system and incomplete primary immunisation 10…”

Fc Glycan-Mediated Regulation of Placental Antibody Transfer

“…However, vaccines have been less effective at reducing infection-related deaths in newborns (Amenyogbe et al, 2015). Compromised vaccine-induced immunity in infants has been attributed to the potentially tolerogenic nature of the neonatal immune system (Yu et al, 2018), the reduced functionality of newborn immune cells (Lee and Lin, 2013;Yu et al, 2018), and dampened immunity from pre-existing maternal antibodies (Saso and Kampmann, 2017). Strategies have been proposed to drive more effective immunity in newborns, including designing vaccines and adjuvants tailored to neonates (Saso and Kampmann, 2017;Whittaker et al, 2018).…”

Aberrant newborn T cell and microbiota developmental trajectories predict respiratory compromise during infancy

“…We next investigated the patterns of individual T cell population abundances over time from birth through one year. Previous studies focusing on a limited number of T cell subsets have suggested a straightforward model in which the fetal T cell developmental program is first biased towards tolerance and hyporesponsiveness, but then acquires, following repeat immune priming postnatally, conventional memory T cells with polarized cytokine functions (19)(20)(21)(22). To more comprehensively characterize the T cell populations that follow a PMA-directed program, we examined populations that were selected as statistical predictors of PMA using elasticnet regression (see "Mistimed Immune and Microbial Development Predict Respiratory Morbidity").…”