BACKGROUND: 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. METHODS: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 μg or 30 μg 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). RESULTS: Both vaccines were well-tolerated. A single 15 μg 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 μg 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 μg 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. CONCLUSION: These trials provided evidence for policymakers that a single 15 μg dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30 μg dose for the elderly.
RCT Entities:
BACKGROUND: 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 H1N1influenza vaccines in independent, but simultaneously conducted, multi-center Phase 2 trials of identical design. METHODS: 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 μg or 30 μg 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). RESULTS: Both vaccines were well-tolerated. A single 15 μg 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 μg 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 μg 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. CONCLUSION: These trials provided evidence for policymakers that a single 15 μg dose of 2009 A/H1N1 vaccine would likely protect most U.S. adults and suggest a potential benefit of a 30 μg dose for the elderly.
Authors: Robert B Couch; Patricia Winokur; Rebecca Brady; Robert Belshe; Wilbur H Chen; Thomas R Cate; Bryndis Sigurdardottir; Amy Hoeper; Irene L Graham; Robert Edelman; Fenhua He; Diane Nino; Jose Capellan; Frederick L Ruben Journal: Vaccine Date: 2007-09-14 Impact factor: 3.641
Authors: Michael E Greenberg; Michael H Lai; Gunter F Hartel; Christine H Wichems; Charmaine Gittleson; Jillian Bennet; Gail Dawson; Wilson Hu; Connie Leggio; Diane Washington; Russell L Basser Journal: N Engl J Med Date: 2009-09-10 Impact factor: 91.245
Authors: T Rowe; R A Abernathy; J Hu-Primmer; W W Thompson; X Lu; W Lim; K Fukuda; N J Cox; J M Katz Journal: J Clin Microbiol Date: 1999-04 Impact factor: 5.948
Authors: Wendy A Keitel; Robert L Atmar; Thomas R Cate; Nancy J Petersen; Stephen B Greenberg; Fred Ruben; Robert B Couch Journal: Arch Intern Med Date: 2006-05-22
Authors: Sharon E Frey; David I Bernstein; Rebecca C Brady; Wendy A Keitel; Hana El Sahly; Nadine Georges Rouphael; Mark J Mulligan; Robert L Atmar; Srilatha Edupuganti; Shital M Patel; Michelle Dickey; Irene Graham; Edwin L Anderson; Diana L Noah; Heather Hill; Mark Wolff; Robert B Belshe Journal: Vaccine Date: 2014-11-11 Impact factor: 3.641
Authors: Karen L Kotloff; Natasha B Halasa; Christopher J Harrison; Janet A Englund; Emmanuel B Walter; James C King; C Buddy Creech; Sara A Healy; Rowena J Dolor; Ina Stephens; Kathryn M Edwards; Diana L Noah; Heather Hill; Mark Wolff Journal: Pediatr Infect Dis J Date: 2014-08 Impact factor: 2.129
Authors: Wendy A Keitel; Lisa A Jackson; Srilatha Edupuganti; Patricia L Winokur; Mark J Mulligan; Natalie J Thornburg; Shital M Patel; Nadine G Rouphael; Lilin Lai; Sandhya Bangaru; Monica M McNeal; Abbie R Bellamy; Heather R Hill Journal: J Infect Dis Date: 2015-02-03 Impact factor: 5.226
Authors: Wilbur H Chen; Lisa A Jackson; Kathryn M Edwards; Wendy A Keitel; Heather Hill; Diana L Noah; C Buddy Creech; Shital M Patel; Brian Mangal; Karen L Kotloff Journal: Open Forum Infect Dis Date: 2014-10-08 Impact factor: 3.835
Authors: Sara P H van den Berg; Albert Wong; Marion Hendriks; Ronald H J Jacobi; Debbie van Baarle; Josine van Beek Journal: Front Immunol Date: 2018-01-29 Impact factor: 7.561