Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study

Abstract

Background. Highly pathogenic avian influenza H5N1 viruses remain a threat to human health, with potential to become pandemic agents.Methods. This phase III, placebo-controlled, observer-blinded study evaluated the immunogenicity, cross-reactivity, safety, and lot consistency of 2 doses of oil-in-water (AS03A) adjuvanted H5N1 A/Indonesia/05/2005 (3.75 μg hemagglutinin antigen) prepandemic candidate vaccine in 4561 adults aged 18–91 years.Results. Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for pandemic vaccines in all age strata 21 days after the second dose. At 6 months after the administration of the primary dose, serum antibody seroconversion rates continued to fulfill licensure criteria. Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004. Consistency was demonstrated for 3 consecutive H5N1 vaccine lots. Temporary injection-site pain was more frequent with H5N1 vaccine than placebo (89.3% and 70.7% in the 18–64 and ≥65 years strata vs 22.2% and 14.4% in the placebo groups). Unsolicited adverse event frequency, including medically attended and serious events, was similar between groups through day 364.Conclusions. In adults and elderly adults, AS03A-adjuvanted H5N1 candidate vaccine was highly immunogenic for A/Indonesia/05/2005, with cross-reactivity against A/Vietnam/1194/2004. Temporary injection site reactions were more frequent with H5N1 vaccine than placebo, although the H5N1 vaccine was well tolerated overall.Clinical Trials Registration. NCT00616928.

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis

“…Indeed, the AS03 adjuvant present in some vaccines promotes immunogenicity by modulating the expression of local cytokines and by increasing the antigen loading in monocytes (17). Although this adjuvant has been safely administered with the H1N1 and the H5N1 strains to thousands of healthy adults (18), more data are needed about the potential for allosensitization among patients with renal disease. Indeed, many reports show that de novo occurrence of posttransplant anti-HLA Abs is associated with chronic rejection and graft loss (19 -21).…”

Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review

“…Other trials have reported a low incidence of adverse effects (0%-3%) and no significant difference in serious adverse events between influenza vaccine and placebo. [15][16][17] Of the RCTs, FLUCAD 31 was likely the most well designed. The authors attempted to minimize bias and confounding through appropriate randomization, use of intention-to-treat analyses, and minimal loss to follow-up.…”

“…14 However, in prospective randomized trials that included CV outcomes for safety assessment, influenza vaccination was not associated with a reduction in CV events, [15][16][17][18] although these trials were limited by low event rates and potential for misclassification. 19 Both the American Heart Association/American College of Cardiology and the European Society of Cardiology recommend the influenza vaccine annually for individuals with established CVD [20][21][22] without specifically stating that the purpose is to reduce the risk of CV events.…”

Low hemagglutinin antigen dose influenza vaccines adjuvanted with AS03 alter the long-term immune responses in BALB/c mice

“…6,[10][11][12] The pandemic experience created the unusual situation in which much of what we know about the immunological impact of AS03 is derived from human studies. This body of work has demonstrated that AS03-adjuvanted, dose-sparing formulations can induce strong serum antibody responses that persist for at least 12 months in healthy children, [13][14][15][16][17] adults [18][19][20][21][22][23] and the elderly, [24][25][26] and that influenza-specific, poly-functional CD4C T cells can be detected in human PBMC samples for at least 6 months after vaccination. [27][28][29] We have previously shown that AS03 can induce powerful humoral 6,12 and cellular responses 6 to influenza antigens over a surprisingly wide range of Ag doses (100-to 1000-fold lower than a 'standard' 3 mg HA dose in mice) at 3 weeks after a booster immunization The objective of this study was to determine the persistence of these responses up to 34 weeks after LD-AS03-adjuvanted vs. HD-unadjuvanted vaccination.…”