Long-term outcome of the humoral and cellular immune response of an H5N1 adjuvanted influenza vaccine in elderly persons: 2-year follow-up of a randomised open-label studyReport as inadecuate




Long-term outcome of the humoral and cellular immune response of an H5N1 adjuvanted influenza vaccine in elderly persons: 2-year follow-up of a randomised open-label study - Download this document for free, or read online. Document in PDF available to download.

Trials

, 15:419

First Online: 29 October 2014Received: 31 October 2013Accepted: 14 October 2014DOI: 10.1186-1745-6215-15-419

Cite this article as: Gillard, P., Giet, D., Heijmans, S. et al. Trials 2014 15: 419. doi:10.1186-1745-6215-15-419

Abstract

BackgroundOlder individuals often have a reduced immune response to influenza vaccination, which might be improved by administering a higher vaccine dose. We compared the immune response to two single doses of the AS03A-adjuvanted H5N1 pandemic vaccine 3.75 μg hemagglutinin of A-Vietnam-1194-2004 with that of two double vaccine doses 7.5 μg hemagglutinin in adults aged ≥61 years. Here we report the 2-year persistence of the humoral and cellular immune response.

MethodsIn this phase II, open-label study, healthy participants aged 61 to 88 years median 68 years were randomised 3:1:3:1 to receive two single doses of the AS03A-adjuvanted vaccine 1xH5N1-AS or the non-adjuvanted vaccine 1xH5N1, or two double doses of the AS03A-adjuvanted vaccine 2xH5N1-AS or the non-adjuvanted vaccine 2xH5N1, 21 days apart. Serum haemagglutination inhibition antibodies and cellular immune responses against A-Vietnam-1194-2004 were measured in all groups at months 12 and 24; neutralising antibodies were assessed in a subset of the adjuvanted groups. Serious adverse events and adverse events of specific interest were recorded.

ResultsAt month 24, haemagglutination inhibition antibody seroprotection rates were 37.2% 95% CI 27.0% to 48.3% for 1xH5N1-AS, 30.9% 95% CI 21.1% to 42.1% for 2xH5N1-AS, 16.2% 95% CI 6.2% to 32.0% for 1xH5N1, and 8.3% 95% CI 1.0% to 27.0% for 2xH5N1. Haemagglutination inhibition antibody geometric mean titres were 17.6 95% CI 13.7 to 22.5 for 1xH5N1-AS, 18.4 95% CI 14.2 to 23.8 for 2xH5N1-AS, 12.3 95% CI 8.9 to 16.9 for 1xH5N1 and 9.8 95% CI 6.7 to 14.4 for 2xH5N1. The median frequency of antigen-specific CD4 T cells per 10 T cells 25th quartile; 75th quartile was 852 482; 1477 for 1xH5N1-AS, 1147 662; 1698 for 2xH5N1-AS, 556 343; 749 for 1x-H5N1 and 673 465; 1497 for 2xH5N1. Neutralising antibody geometric mean titres were 391.0 95% CI 295.5 to 517.5 in the 1xH5N1-AS group and 382.8 95% CI 317.4 to 461.6 in the 2xH5N1-AS group.

ConclusionsAntibody levels declined substantially in all groups. Seroprotection rates, geometric mean titres for haemagglutination inhibition antibodies, and CD4 T-cell responses tended to be higher in the AS03A-adjuvanted groups. There was no clear benefit, in terms of long-term persistence of the immune response, of doubling the dose of the adjuvanted vaccine. No safety concern was observed up to 24 months post-primary vaccination.

Trial registrationNCT00397215 7 November 2006.

KeywordsAvian influenza H5N1 Pre-pandemic vaccine Persistence Elderly population Cell-mediated immune response AbbreviationsAESIadverse events of specific interest

ATPaccording-to-protocol

CHMPCommittee for Human Medicinal Products

GMTgeometric mean titre

HIhaemagglutination inhibition

SAEserious adverse event

SCRseroconversion rate

SPRseroprotection rate.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6215-15-419 contains supplementary material, which is available to authorized users.

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Author: Paul Gillard - Didier Giet - Stéphane Heijmans - Mamadou Dramé - Karl Walravens - François Roman

Source: https://link.springer.com/







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