Rapid immunization against H5N1: a randomized trial evaluating homologous and cross-reactive immune responses to AS03(A)-adjuvanted vaccination in adults

Benjamin Lasko, Dennis Reich, Anuradha Madan, François Roman, Ping Li, David Vaughn, Benjamin Lasko, Dennis Reich, Anuradha Madan, François Roman, Ping Li, David Vaughn

Abstract

Background: Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03(A)-adjuvanted H5N1 vaccine.

Methods: This phase II, open-label, 6-month study randomized participants (aged 18-64 years) to 2 vaccine doses administered 21 (standard schedule), 14, or 7 days apart, or on the same day. Coprimary end points were that the lower limit of the 98.75% confidence interval 14 days after the last dose must be (1) >40% for seroconversion rate (SCR) (Center for Biologics Evaluation and Research [CBER] criterion) and (2) >50% for seroprotection rate (SPR) (attainment rate for reciprocal hemagglutination inhibition titers ≥40, protocol-defined criterion) for the vaccine homologous strain (A/Indonesia/5/2005). European Committee for Human Medicinal Products (CHMP) immunogenicity criteria were also evaluated.

Results: Coprimary end points were achieved (lower 98.75% confidence intervals exceeded defined values). Titers were highest with the standard schedule. Nevertheless, CBER SCR, protocol-defined SPR, and CHMP criteria were met with all schedules for the A/Indonesia/5/2005 strain. There were no significant differences between age groups (18-40 vs 41-64 years). Immune response was robust against drift variants A/turkey/Turkey/1/2005 and A/Vietnam/1194/2004.

Conclusions: The AS03(A)-adjuvanted H5N1 vaccine in accelerated schedules offers a robust immune response against vaccine homologous and drift variant strains, allowing consideration of compressed vaccination intervals.

Clinical trials registration: NCT00695669.

Figures

Figure 1.
Figure 1.
Disposition of participants. ATP, according-to-protocol cohort; TVC, total vaccinated cohort.
Figure 2.
Figure 2.
Hemagglutination inhibition geometric mean titers (GMTs) against (A) A/Indonesia/5/2005 H5N1, (B) A/Vietnam/1194/2004 H5N1, and (C) A/turkey/Turkey/1/2005 H5N1 at day 0 through 42. Data are presented for the according-to-protocol cohort (participants aged 18–64 years). Vaccine doses were administered at intervals of 21 days (group 0/21), 14 days (group 0/14), or 7 days (group 0/7) or on the same day (group 0/0). CI, confidence interval.
Figure 3.
Figure 3.
Hemagglutination inhibition geometric mean titers (GMTs) against A/Indonesia/5/2005 H5N1 at day 0 through 42 according to age: (A) 18–40 years vs (B) 41–64 years. Data are presented for according-to-protocol cohort. Vaccine doses were administered at intervals of 21 days (group 0/21), 14 days (group 0/14), or 7 days (group 0/7) or on the same day (group 0/0). CI, confidence interval.

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Source: PubMed

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