Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial

Nicholson, Karl G.; Abrams, Keith R.; Batham, Sally; Clark, Tristan; Höschler, Katja; Lim, Wei Shen; Medina, Marie-Jo; Nguyen-Van-Tam, Jonathan S.; Read, Robert C.; Warren, Fiona C; Zambon, Maria

doi:10.1016/s1473-3099(10)70296-6

Cited by 89 publications

(70 citation statements)

References 30 publications

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“…These formulations elicited very different antigen-specific cytokine/chemokine profiles and patterns of antigen-specific CD4C T cells in re-stimulated splenocytes compared to the HD-unadjuvanted vaccine. Our results confirm the dose-sparing potential of AS03 that has already been demonstrated in the human experience with the AS03-adjuvated pH1N1 vaccine 13,15,16,18,19,24,26 and provide reassurance that this response does not appear to come at the expense of long-term memory. However, there is likely an optimal level of any given antigen (C adjuvant) that will elicit and maintain a multi-faceted immune response.…”

Section: Discussionsupporting

confidence: 88%

“…6,[10][11][12] The pandemic experience created the unusual situation in which much of what we know about the immunological impact of AS03 is derived from human studies. This body of work has demonstrated that AS03-adjuvanted, dose-sparing formulations can induce strong serum antibody responses that persist for at least 12 months in healthy children, [13][14][15][16][17] adults [18][19][20][21][22][23] and the elderly, [24][25][26] and that influenza-specific, poly-functional CD4C T cells can be detected in human PBMC samples for at least 6 months after vaccination. [27][28][29] We have previously shown that AS03 can induce powerful humoral 6,12 and cellular responses 6 to influenza antigens over a surprisingly wide range of Ag doses (100-to 1000-fold lower than a 'standard' 3 mg HA dose in mice) at 3 weeks after a booster immunization The objective of this study was to determine the persistence of these responses up to 34 weeks after LD-AS03-adjuvanted vs. HD-unadjuvanted vaccination.…”

Section: Discussionmentioning

confidence: 99%

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Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Yam

Brewer

Bleau

et al. 2016

Human Vaccines & Immunotherapeutics

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We investigated the long-term immune profiles of dose-sparing, AS03-adjuvanted vaccines compared to a traditional high-dose, unadjuvated influenza vaccine formulation. BALB/c mice received 2 IM injections of influenza A/Uruguay/716/2007 (H3N2) split vaccine antigen: high-dose (HD) (3 mg hemagglutinin (HA)/ dose) or low-dose (LD) formulations (0.03 mg or 0.003 mg HA) with AS03 and were followed to 34 weeks post-boost (pb). We examined serologic responses, spleen and bone marrow (BM) HA-specific antibodysecreting cells (ASCs) by ELISpot, influenza-specific cytokine/chemokine production in re-stimulated splenocytes by multiplex ELISA, and antigen-specific CD4C T cells that express cytokines (IL-2, IFNg, TNFa and IL-5) by flow cytometry. All formulations elicited robust serum antibody titers that persisted for at least 34 weeks. The number of antigen-specific ASCs in the spleen and BM were higher in the 2 LD CAS03 groups, but despite having fewer ASCs, the average spot size in the HD-unadjuvanted group was larger at later time-points, suggesting greater antibody production per cell. Striking differences in the long-term profiles induced by the different vaccine formulations may contribute to these different ASC profiles. The HD-unadjuvanted vaccine elicited strong Th2 cytokines during the first 6 weeks pb but LDCAS03 groups generated broader, more durable responses at later timepoints. Finally, the 0.03 mg HACAS03 group generated the greatest number of antigen-specific CD4C T cells and the highest percentage of polyfunctional cells that expressed 2 or more cytokines. Although all of the tested vaccines induced durable antibody responses, we show that different vaccine formulations (dose-sparing, adjuvant) generate distinct long-term immune profiles. Furthermore, our data suggest that the different profiles may be generated through unique mechanisms.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Yam

Brewer

Bleau

et al. 2016

Human Vaccines & Immunotherapeutics

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“…The studies evaluating the influenza H5N1 vaccine containing the adjuvant AS03 have associated its presence with an increase in vaccine reactogenicity (Leroux-Roels et al 2007, Baras et al 2008, Rümke et al 2008) and trials conducted with the AS03-adjuvanted H1N1 pandemic vaccine also found high rates of adverse events. Local mild to moderate reactions were more common and serious adverse events were rarely reported (Carmona et al 2010, Roman et al 2010a, b, Waddington et al 2010, Nicholson et al 2011.…”

Section: Discussionmentioning

confidence: 97%

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

Cerbino-Neto

Santos

Gouvêa

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…25 Both vaccines were found to be statistically significantly more immunogenic in adults from 18 to 44 years of age than in older individuals. This study assessed the persistence of antibody 6 months after vaccination.…”

Section: Response To Monovalent Pandemic Influenza Vaccinementioning

confidence: 92%

A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children

Whalley

Walker²,

Snape³

et al. 2011

Health Technol Assess

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How to obtain copies of this and other HTA programme reports An electronic version of this title, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (www.hta.ac.uk). A fully searchable DVD is also available (see below).Printed copies of HTA journal series issues cost £20 each (post and packing free in the UK) to both public and private sector purchasers from our despatch agents.Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per issue and for the rest of the world £3 per issue. How to order:-fax (with credit card details) -post (with credit card details or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you to either print out your order or download a blank order form. Contact details are as follows:Synergie UK (HTA Department) Digital House, The Loddon Centre Wade Road Basingstoke Hants RG24 8QW Email: orders@hta.ac.uk Tel: 0845 812 4000 -ask for 'HTA Payment Services' (out-of-hours answer-phone service) Fax: 0845 812 4001 -put 'HTA Order' on the fax header Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to University of Southampton and drawn on a bank with a UK address.Paying by credit card You can order using your credit card by phone, fax or post. SubscriptionsNHS libraries can subscribe free of charge. Public libraries can subscribe at a reduced cost of £100 for each volume (normally comprising 40-50 titles). The commercial subscription rate is £400 per volume (addresses within the UK) and £600 per volume (addresses outside the UK). Please see our website for details. Subscriptions can be purchased only for the current or forthcoming volume.How do I get a copy of HTA on DVD?Please use the form on the HTA website (www.hta.ac.uk/htacd/index.shtml). HTA on DVD is currently free of charge worldwide.The website also provides information about the HTA programme and lists the membership of the various committees. HTAA 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children Declaration of competing interests: Vaccines used in the original study were manufactured by GlaxoSmithKline and Baxter, both of which donated the vaccine, but had no role in study planning or conduct. The vaccine used in this follow-on study was manufactured by GlaxoSmithKline, from whom it was purchased. AJP, AF, PTH and SF act as chief or principal investigators for clinical trials conducted on behalf of their respective NHS trusts and/or universities, sponsored by vaccine manufacturers, but receive no personal payments from them. KH has been an investigator for clinical trials sponsored by vaccine manufacturers, but received no personal payments from them. AJP, AF, PTH and SF have participated in advisory boards for vaccine manufacturers, but receive no personal payments for this work. MDS, PTH, SF, KH and AF have received financial assistance from vaccin...

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Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial

Cited by 89 publications

References 30 publications

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

Comparison of adverse events following immunization with pandemic influenza A (H1N1)pdm09 vaccine with or without adjuvant among health professionals in Rio de Janeiro, Brazil

A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children

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