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Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009.

ABSTRACT: The influenza A/H1N1 pandemic in 2009 created an urgent need to develop vaccines for mass immunization. To guide decisions regarding the optimal immunization dosage and schedule for adults, we evaluated two monovalent, inactivated, unadjuvanted H1N1 influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design.Healthy adults, stratified by age (18-64 years and ?65 years), were randomized (1:1 allocation), in a double-blind, parallel-group design, to receive two intramuscular doses (21 days apart) of vaccine containing approximately 15 ?g or 30 ?g of hemagglutinin (HA). Primary endpoints were safety (reactogenicity for 8 days after each vaccination and vaccine-associated serious adverse events during the 7 month study) and immunogenicity (proportion of subjects, stratified by age, achieving a serum hemagglutination inhibition [HI] antibody titer ?1:40 or a ?4-fold rise in titer after a single injection of either dosage).Both vaccines were well-tolerated. A single 15 ?g dose induced HI titers ?1:40 in 90% of younger adults (95% confidence interval [CI] 82-95%) and 81% of elderly (95% CI 71-88%) who received Sanofi-Pasteur vaccine (subsequently found to contain 24 ?g HA in the standard potency assay), and in 80% of younger adults (95% CI 71-88%) and 60% of elderly (95% CI 50-70%) who received CSL vaccine. Both vaccines were significantly more immunogenic in younger compared with elderly adults by at least one endpoint measure. Increasing the dose to 30 ?g raised the frequency of HI titers ?1:40 in the elderly by approximately 10%. Higher dosage did not significantly enhance immunogenicity in younger adults and a second dose provided little additional benefit to either age group.These trials provided evidence for policymakers that a single 15 ?g dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30 ?g dose for the elderly.

SUBMITTER: Chen WH

PROVIDER: S-EPMC3490194 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009.

Chen Wilbur H WH Winokur Patricia L PL Edwards Kathryn M KM Jackson Lisa A LA Wald Anna A Walter Emmanuel B EB Noah Diana L DL Wolff Mark M Kotloff Karen L KL

Vaccine 20120423 28

<h4>Background</h4>The influenza A/H1N1 pandemic in 2009 created an urgent need to develop vaccines for mass immunization. To guide decisions regarding the optimal immunization dosage and schedule for adults, we evaluated two monovalent, inactivated, unadjuvanted H1N1 influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design.<h4>Methods</h4>Healthy adults, stratified by age (18-64 years and ≥65 years), were randomized (1:1 allocation), in a ...[more]

PMID: 22537984

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Project description:BACKGROUND:Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation. METHODS:We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis. RESULTS:Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (>?=?70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses <?=?6 µg (even with as little as 1.875 µg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines. CONCLUSIONS:Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed.

Dataset Information

Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009.

Publications

Phase 2 assessment of the safety and immunogenicity of two inactivated pandemic monovalent H1N1 vaccines in adults as a component of the U.S. pandemic preparedness plan in 2009.

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