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 studyReportar como inadecuado

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, 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


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


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

Fuente: https://link.springer.com/

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