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 6,6ʹ-dibehenate. Such compounds make interesting neonatal adjuvant candidates, either used alone or in combination with traditional innate immune adjuvants.

KEYWORDS:

• Neonate
• immunity
• vaccine
• adjuvant
• Advax
• delta inulin
• carbohydrate
• influenza

Article Highlights

• Influenza and RSV infections cause high morbidity in neonates, requiring better vaccines

• Neonatal responses to non-living vaccines are low and unprotective

• Live BCG vaccines that are effective in neonates express immune activators including trehalose-6,6-dimycolate

• Multidose Hepatitis B and polio vaccine regimens have shown benefit when the first dose is given to neonates

• Sugar-based adjuvants including delta inulin (Advax), curdlan and trehalose 6,6ʹ-dibehenate enhance neonatal vaccine responses

• Such sugar-based adjuvants may help solve the need for neonatal influenza and RSV vaccines

Declaration of interest

I Sakala is an employee of Vaxine Pty Ltd, which developed the Advax adjuvant, and is an academic affiliate of the Flinders University. N Petrovsky is the founder and Research Director of Vaxine Pty Ltd, and is an academic affiliate of the Flinders University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800039C and Collaborative Research Contact No. U01AI061142 (to NP), and Clinical and translational Science Institute award TL1 TR001858 (to Katherine ME). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.