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 random

[tetano]

Trials. 2014 Oct 29;15(1):419. [Epub ahead of print]
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.
Gillard P, Giet D, Heijmans S, Dram? M, Walravens K, Roman F.
Abstract
BACKGROUND:

Older 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 mug hemagglutinin of A/Vietnam/1194/2004) with that of two double vaccine doses (7.5 mug hemagglutinin) in adults aged >=61 years. Here we report the 2-year persistence of the humoral and cellular immune response.
METHODS:

In 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.
RESULTS:

At 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 106 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.
CONCLUSIONS:

Antibody 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 registration: NCT00397215 (7 November 2006).

PMID:
25354581
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/25354581

 

[Vibrant62]

Re: 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

The above data indicates that an annual vaccination with H5N1 vaccine would be required to maintain immunity at a level that would protect against infection in this 60+ age group, and that higher vaccine doses would not result in increased levels of 24 month immunity.

I wonder if the study has been extended to study the effects of annual revaccination, and if repeated exposures over a longer time period produces a more long lasting immunogenic effect.

Annual vaccination would present very significant challenges in terms of mass production of vaccines in the event of a pandemic (which would be unable to produce adequate annual volumes for the global population as things currently stand).