Limits...
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, Dramé M, Walravens K, Roman F - Trials (2014)

Bottom Line: Serious adverse events and adverse events of specific interest were recorded.There was no clear benefit, in terms of long-term persistence of the immune response, of doubling the dose of the adjuvanted vaccine.NCT00397215 (7 November 2006).

View Article: PubMed Central - PubMed

Affiliation: GSK Vaccines, Wavre, Belgium. paul.gillard@gsk.com.

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 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.

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).

Show MeSH

Related in: MedlinePlus

Neutralising antibody response against the heterologous A/Indonesia/05/2005 strain in the AS03A-adjuvanted groups. Vaccination groups are: 1xH5N1-AS, single dose of the AS03A-adjuvanted vaccine; 1xH5N1, single dose of the non-adjuvanted vaccine; 2xH5N1-AS, double dose of the AS03A-adjuvanted vaccine; 2xH5N1, double dose of the non-adjuvanted vaccine. Seroconversion rate (SCR) was defined as the percentage of vaccinees with a ≥4-fold increase in neutralising antibody titre at post-vaccination. GMT, geometric mean titre. Error bars indicate the 95% confidence intervals. Post-vaccination = day 42. Post-vaccination results are shown for a subset of the according-to-protocol immunogenicity cohort (1xH5N1-AS: N =87, 2xH5N1-AS: N =82), month 12 and month 24 results for a subset of the month 24 according-to-protocol persistence cohort (1xH5N1-AS: N =51, 2xH5N1-AS: N =54); N = maximum number of participants with available results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4233031&req=5

Fig5: Neutralising antibody response against the heterologous A/Indonesia/05/2005 strain in the AS03A-adjuvanted groups. Vaccination groups are: 1xH5N1-AS, single dose of the AS03A-adjuvanted vaccine; 1xH5N1, single dose of the non-adjuvanted vaccine; 2xH5N1-AS, double dose of the AS03A-adjuvanted vaccine; 2xH5N1, double dose of the non-adjuvanted vaccine. Seroconversion rate (SCR) was defined as the percentage of vaccinees with a ≥4-fold increase in neutralising antibody titre at post-vaccination. GMT, geometric mean titre. Error bars indicate the 95% confidence intervals. Post-vaccination = day 42. Post-vaccination results are shown for a subset of the according-to-protocol immunogenicity cohort (1xH5N1-AS: N =87, 2xH5N1-AS: N =82), month 12 and month 24 results for a subset of the month 24 according-to-protocol persistence cohort (1xH5N1-AS: N =51, 2xH5N1-AS: N =54); N = maximum number of participants with available results.

Mentions: All participants in the adjuvanted groups remained seropositive for neutralising antibodies against A/Vietnam/1194/2004 at both month 12 and month 24, with a decrease in antibody GMTs and SCRs compared to 3 weeks post-vaccination (Figure 4A,B). The antibody GMTs remained higher than the pre-vaccination values, which were 131.8 (95% CI 95.4 to 182.1) for the 1xH5N1-AS group and 115.6 (95% CI 90.0 to 148.4) for the 2xH5N1-AS group.Most participants (≥84.1%) remained seropositive for neutralising antibodies against the heterologous A/Indonesia/05/2005 strain, with a decrease in antibody GMTs at both month 12 and month 24 (Figure 5). Pre-vaccination GMTs were 50.4 (95% CI 38.6 to 65.8) for 1xH5N1-AS and 36.6 (95% CI 27.8 to 48.1) for 2xH5N1-AS.Figure 4


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, Dramé M, Walravens K, Roman F - Trials (2014)

Neutralising antibody response against the heterologous A/Indonesia/05/2005 strain in the AS03A-adjuvanted groups. Vaccination groups are: 1xH5N1-AS, single dose of the AS03A-adjuvanted vaccine; 1xH5N1, single dose of the non-adjuvanted vaccine; 2xH5N1-AS, double dose of the AS03A-adjuvanted vaccine; 2xH5N1, double dose of the non-adjuvanted vaccine. Seroconversion rate (SCR) was defined as the percentage of vaccinees with a ≥4-fold increase in neutralising antibody titre at post-vaccination. GMT, geometric mean titre. Error bars indicate the 95% confidence intervals. Post-vaccination = day 42. Post-vaccination results are shown for a subset of the according-to-protocol immunogenicity cohort (1xH5N1-AS: N =87, 2xH5N1-AS: N =82), month 12 and month 24 results for a subset of the month 24 according-to-protocol persistence cohort (1xH5N1-AS: N =51, 2xH5N1-AS: N =54); N = maximum number of participants with available results.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4233031&req=5

Fig5: Neutralising antibody response against the heterologous A/Indonesia/05/2005 strain in the AS03A-adjuvanted groups. Vaccination groups are: 1xH5N1-AS, single dose of the AS03A-adjuvanted vaccine; 1xH5N1, single dose of the non-adjuvanted vaccine; 2xH5N1-AS, double dose of the AS03A-adjuvanted vaccine; 2xH5N1, double dose of the non-adjuvanted vaccine. Seroconversion rate (SCR) was defined as the percentage of vaccinees with a ≥4-fold increase in neutralising antibody titre at post-vaccination. GMT, geometric mean titre. Error bars indicate the 95% confidence intervals. Post-vaccination = day 42. Post-vaccination results are shown for a subset of the according-to-protocol immunogenicity cohort (1xH5N1-AS: N =87, 2xH5N1-AS: N =82), month 12 and month 24 results for a subset of the month 24 according-to-protocol persistence cohort (1xH5N1-AS: N =51, 2xH5N1-AS: N =54); N = maximum number of participants with available results.
Mentions: All participants in the adjuvanted groups remained seropositive for neutralising antibodies against A/Vietnam/1194/2004 at both month 12 and month 24, with a decrease in antibody GMTs and SCRs compared to 3 weeks post-vaccination (Figure 4A,B). The antibody GMTs remained higher than the pre-vaccination values, which were 131.8 (95% CI 95.4 to 182.1) for the 1xH5N1-AS group and 115.6 (95% CI 90.0 to 148.4) for the 2xH5N1-AS group.Most participants (≥84.1%) remained seropositive for neutralising antibodies against the heterologous A/Indonesia/05/2005 strain, with a decrease in antibody GMTs at both month 12 and month 24 (Figure 5). Pre-vaccination GMTs were 50.4 (95% CI 38.6 to 65.8) for 1xH5N1-AS and 36.6 (95% CI 27.8 to 48.1) for 2xH5N1-AS.Figure 4

Bottom Line: Serious adverse events and adverse events of specific interest were recorded.There was no clear benefit, in terms of long-term persistence of the immune response, of doubling the dose of the adjuvanted vaccine.NCT00397215 (7 November 2006).

View Article: PubMed Central - PubMed

Affiliation: GSK Vaccines, Wavre, Belgium. paul.gillard@gsk.com.

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 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.

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).

Show MeSH
Related in: MedlinePlus