Neonatal vaccine effectiveness and the role of adjuvants

Abstract

Introduction: Neonates are less responsive to vaccines than adults, making it harder to protect newborns against infection. Neonatal differences in antigen-presenting cell, B and T cell function, all likely contribute. A key question is whether novel adjuvants might be able to make neonatal vaccines more effective. Areas covered: This review addresses the issues of how to improve neonatal vaccines, which we have defined as vaccines given in the first 4 weeks of life in a human infant or the first week of life in a mouse. A search was performed using keywords including 'neonatal immunity', 'neonatal immunisation', 'vaccine' and 'adjuvant' of PubMed articles published between 1960 and 2018. Expert opinion: Sugar-like structures have recently been shown to prime the infant adaptive immune system to respond to vaccines, being potentially more effective than traditional adjuvants. Sugar-based compounds with beneficial adjuvant effects in neonatal vaccine models include delta inulin (Advax), curdlan, and trehalose 6,6'-dibehenate. Such compounds make interesting neonatal adjuvant candidates, either used alone or in combination with traditional innate immune adjuvants.

Keywords: Advax; Neonate; adjuvant; carbohydrate; delta inulin; immunity; influenza; vaccine.

Figure 1.

Challenges to neonatal immunization related to characteristics of the newborn immune system. Differences in the neonatal immune system have an effect on increased susceptibility to infection and decreased vaccine efficacy. The recognition of infectious agents is reduced in early life and it is therefore easier for a pathogen to invade the host. Neonates are also less experienced so have no immune memory against infection. (2) Decreased vaccine efficacy. In a similar fashion to infection, reduced recognition of vaccine antigens as foreign means that induction of protective memory responses to vaccines are reduced. There is also an effect of maternally derived antibody that may mask key epitopes of the vaccine. Therefore, a successful vaccine formulation should be able to circumvent or overcome the functional peculiarities of the neonatal period. Abbreviations: APC = Antigen-presenting cells. (Refs [13,16,27]).

Figure 2.

Overcoming functional differences in neonatal immune system through use of vaccine adjuvants. Adjuvants enhance immunogenicity of neonatal vaccines through innate activation and via enhancement of multiple aspects of adaptive immunity. Adjuvants can activate APC, such as monocytes and dendritic cells and increase cytokine production and co-stimulatory marker expression, which improve the priming of naïve CD4⁺ T cells. Following activation and antigen presentation, CD4⁺ T cells can differentiate into T follicular helper cells, which are necessary in the germinal center reaction to assist B cells in generating effective antibodies. Improvement in memory and plasma B cells enhances antigen detection and neutralization through increased production of high-affinity antibodies. Abbreviations/key to understanding: TLR = Toll-like receptor; CpG-ODN = CpG-oligodeoxynucleotides; MPLA = Monophosphoryl lipid A; DDA/TDB = dimethyldioctadecyl ammonium (DDA) and trehalose 6,6′-dibehenate (TDB); 3M-052-SE = a TLR7/8 agonist containing imidazoquinoline/Oil-in-water squalene emulsion (SE); Advax = delta inulin adjuvant.