Neonatal Vaccination: Challenges and Intervention Strategies

Abstract

Background: While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges.

Objective: This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines.

Methods: We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines.

Results: Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants.

Conclusion: Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates.

Figure 1

Important cellular interactions during vaccination. The vaccine antigen, in conjunction with TLR ligands and a carrier molecule, promotes secretion of IL-12 and IFNα by DC, which promote T_H1 and CTL proliferation and IgG secretion.

Figure 2

Proposed mechanism of neonatal APC deficiencies. Surface-expressed TLRs require the activity of CD14 for effective signal transduction, while the endosomal TLRs (TLR3, TLR7, and TLR8) are CD14-independent, and can drive effective expression of IL-12 and IFNα in the neonate where CD14 expression is reduced.