Cargando…

Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection

Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior influenza virus exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a m...

Descripción completa

Detalles Bibliográficos
Autores principales: Honda-Okubo, Yoshikazu, Ong, Chun Hao, Petrovsky, Nikolai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. Published by Elsevier Ltd. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562881/
https://www.ncbi.nlm.nih.gov/pubmed/26232344
http://dx.doi.org/10.1016/j.vaccine.2015.07.051
_version_ 1782389215364907008
author Honda-Okubo, Yoshikazu
Ong, Chun Hao
Petrovsky, Nikolai
author_facet Honda-Okubo, Yoshikazu
Ong, Chun Hao
Petrovsky, Nikolai
author_sort Honda-Okubo, Yoshikazu
collection PubMed
description Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior influenza virus exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness. We first tested whether it was possible to use Advax to obtain single-dose vaccine protection of neonatal pups against lethal influenza infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single subcutaneous immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels and was associated with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells. Pups immunized with Advax had significantly higher splenocyte influenza-stimulated IFN-γ, IL-2, IL-4, and IL-10 production by CBA and a 3–10 fold higher frequency of IFN-γ, IL-2, IL-4 or IL-17 secreting T cells by ELISPOT. Immunization with iH1N1 + Advax induced robust protection of pups against virus challenge 3 weeks later, whereas pups immunized with iH1N1 antigen alone had no protection. Protection by Advax-adjuvanted iH1N1 was dependent on memory B cells rather than memory T cells, with no protection in neonatal μMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting ongoing development of Advax™ as a neonatal vaccine adjuvant.
format Online
Article
Text
id pubmed-4562881
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Elsevier Ltd. Published by Elsevier Ltd.
record_format MEDLINE/PubMed
spelling pubmed-45628812016-09-11 Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection Honda-Okubo, Yoshikazu Ong, Chun Hao Petrovsky, Nikolai Vaccine Article Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior influenza virus exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness. We first tested whether it was possible to use Advax to obtain single-dose vaccine protection of neonatal pups against lethal influenza infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single subcutaneous immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels and was associated with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells. Pups immunized with Advax had significantly higher splenocyte influenza-stimulated IFN-γ, IL-2, IL-4, and IL-10 production by CBA and a 3–10 fold higher frequency of IFN-γ, IL-2, IL-4 or IL-17 secreting T cells by ELISPOT. Immunization with iH1N1 + Advax induced robust protection of pups against virus challenge 3 weeks later, whereas pups immunized with iH1N1 antigen alone had no protection. Protection by Advax-adjuvanted iH1N1 was dependent on memory B cells rather than memory T cells, with no protection in neonatal μMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting ongoing development of Advax™ as a neonatal vaccine adjuvant. Elsevier Ltd. Published by Elsevier Ltd. 2015-09-11 2015-07-29 /pmc/articles/PMC4562881/ /pubmed/26232344 http://dx.doi.org/10.1016/j.vaccine.2015.07.051 Text en Copyright © 2015 Elsevier Ltd. Published by Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Honda-Okubo, Yoshikazu
Ong, Chun Hao
Petrovsky, Nikolai
Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title_full Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title_fullStr Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title_full_unstemmed Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title_short Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
title_sort advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562881/
https://www.ncbi.nlm.nih.gov/pubmed/26232344
http://dx.doi.org/10.1016/j.vaccine.2015.07.051
work_keys_str_mv AT hondaokuboyoshikazu advaxdeltainulinadjuvantovercomesimmuneimmaturityinneonatalmicetherebyallowingsingledoseinfluenzavaccineprotection
AT ongchunhao advaxdeltainulinadjuvantovercomesimmuneimmaturityinneonatalmicetherebyallowingsingledoseinfluenzavaccineprotection
AT petrovskynikolai advaxdeltainulinadjuvantovercomesimmuneimmaturityinneonatalmicetherebyallowingsingledoseinfluenzavaccineprotection