Imperial College London
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Dr John S Tregoning

Faculty of Medicine, Department of Infectious Disease

Professor in Vaccine Immunology
 
 
 
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Contact

 

john.tregoning Website

 
 
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Location

 

456 (Shattock Group)Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Russell:2016:10.1128/JVI.03159-15,
author = {Russell, RF and McDonald, JU and Lambert, L and Tregoning, JS},
doi = {10.1128/JVI.03159-15},
journal = {Journal of Virology},
pages = {4735--4744},
title = {Use of the microparticle Nano-SiO2 as an adjuvant to boost vaccine immune responses in neonatal mice against influenza.},
url = {http://dx.doi.org/10.1128/JVI.03159-15},
volume = {90},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example to TLR agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger sensing pathways, focusing on a range of compounds described as inflammasome agonists, including Nanoscale SiO2 (NanoSiO2), Calcium pyrophosphate dihydrate (CPPD) crystals and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants. In vitro these compounds induced an interleukin 1-beta (IL-1β) response in the macrophage-like cell line THP1. In vivo, adult CB6F1 female mice were immunised intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD or M-Tri-DAP and subsequently challenged with H1N1 influenza (A/England/195/2009). The adjuvants boosted anti-haemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2 adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle, but little systemic inflammation measured by serum cytokines. Blocking IL-1β or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting it may work through other pathways than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. IMPORTANCE: Vaccines can fail to protect the most at-risk populations, including the very young, elderly and immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunisation schedules, exacerbated by the failure of vac
AU  - Russell,RF
AU  - McDonald,JU
AU  - Lambert,L
AU  - Tregoning,JS
DO  - 10.1128/JVI.03159-15
EP  - 4744
PY  - 2016///
SN  - 1098-5514
SP  - 4735
TI  - Use of the microparticle Nano-SiO2 as an adjuvant to boost vaccine immune responses in neonatal mice against influenza.
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.03159-15
UR  - http://hdl.handle.net/10044/1/29919
VL  - 90
ER  -
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