Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health.

Eleanor C Semmes,Sallie R Permar,Trevor D Burt,Genevieve G Fouda,Ria Goswami,Jui-Lin Chen

doi:10.3389/fimmu.2020.595297

Abstract

Infants are capable of mounting adaptive immune responses, but their ability to develop long-lasting immunity is limited. Understanding the particularities of the neonatal adaptive immune system is therefore critical to guide the design of immune-based interventions, including vaccines, in early life. In this review, we present a thorough summary of T cell, B cell, and humoral immunity in early life and discuss infant adaptive immune responses to pathogens and vaccines. We focus on the differences between T and B cell responses in early life and adulthood, which hinder the generation of long-lasting adaptive immune responses in infancy. We discuss how knowledge of early life adaptive immunity can be applied when developing vaccine strategies for this unique period of immune development. In particular, we emphasize the use of novel vaccine adjuvants and optimization of infant vaccine schedules. We also propose integrating maternal and infant immunization strategies to ensure optimal neonatal protection through passive maternal antibody transfer while avoiding hindering infant vaccine responses. Our review highlights that the infant adaptive immune system is functionally distinct and uniquely regulated compared to later life and that these particularities should be considered when designing interventions to promote pediatric health.

Highlights

Despite tremendous progress in recent decades, infectious diseases remain a leading cause of morbidity and mortality in pediatric populations worldwide [1,2,3]
Because vaccine-induced protection largely depends on acquired immunity, we have instead focused this review on early life adaptive immunity
We have demonstrated in infant rhesus macaques that extending the interval between human immunodeficiency virus (HIV) immunizations from 3 to 6 weeks increased the durability of antibody responses and promoted the generation of high avidity HIV-specific antibodies [159]

Summary

INTRODUCTION

Despite tremendous progress in recent decades, infectious diseases remain a leading cause of morbidity and mortality in pediatric populations worldwide [1,2,3]. Regulatory T cells (Tregs) maintain fetal immunotolerance in utero and are present in higher numbers and proportions in early life blood and peripheral tissues, which may aid in promoting tolerance to microbial colonization but may impair mucosal and systemic T cell activation and adaptive immune responses. Given the ongoing outbreak of SARS-CoV-2, a newly emergent coronavirus and ongoing infectious threat to pediatric health, it is important to consider how T cell responses may be age-dependent with distinct implications for disease pathogenesis and vaccine interventions [reviewed in [76]] These studies suggest that antigen-specific T cell responses are generated in response to certain pathogens, yet effector T cell responses may be favored over memory T cell responses during early life. Targeted intervention strategies that account for the distinct nature of the neonatal T cell compartment should be employed to effectively engage T cells in adaptive responses

B Cell Development and the Neonatal B Cell Compartment

Findings

CONCLUDING REMARKS