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Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial.

Publication ,  Journal Article
Belshe, RB; Frey, SE; Graham, IL; Anderson, EL; Jackson, LA; Spearman, P; Edupuganti, S; Mulligan, MJ; Rouphael, N; Winokur, P; Dolor, RJ ...
Published in: JAMA
October 8, 2014

IMPORTANCE: The need to respond quickly to potential influenza pandemics is important. Immunologic priming (initial presentation of an antigen to allow antibody responses on revaccination) with vaccine directed toward an older avian influenza H5 strain might lead to secondary antibody responses to a single dose of more current H5 avian influenza vaccine. OBJECTIVES: To assess priming with the older avian influenza A/Vietnam/1203/2004(H5N1) (Vietnam) vaccine and to conduct dose-response studies with vaccine directed against the more contemporary H5N1 avian influenza virus, influenza A/Anhui/01/2005 (Anhui). DESIGN, SETTING, AND PARTICIPANTS: Multicenter US randomized clinical trial beginning in June 2010 with follow-up continuing through October 2011 enrolling 72 healthy adults who were vaccinated 1 year previously with the Vietnam vaccine and 565 vaccine-naive adults. INTERVENTIONS: Participants who were previously vaccinated with 90 µg of unadjuvanted Vietnam vaccine were randomly assigned to receive 3.75 µg of avian influenza Anhui vaccine with or without MF59 adjuvant, stratified by 1 vs 2 previous doses (1 dose: n = 18 with MF59 and n = 17 without; 2 doses: n = 19 with MF59 and n = 18 without). Vaccine-naive individuals were randomly assigned to receive Ahnui vaccine with or without MF59 adjuvant in 1 of 5 doses (3.75 µg [n = 55 with MF59 and n = 59 without], 7.5 µg [n = 51 with MF59 and n = 57 without], 15 µg [n = 48 with MF59 and n = 44 without], 45 µg [n = 47 with MF59 and n = 47 without], or 90 µg [n = 57 without adjuvant]) or placebo (n = 100) given at days 0 and 28. MAIN OUTCOMES AND MEASURES: The primary immunogenicity outcome was hemagglutination inhibition assay (HAI) titer against each vaccine antigen 1 month (day 28) and 6 months (day 180) after last vaccination. The primary safety outcomes were local and systemic adverse events on days 0 to 7 after each vaccination and serious adverse events. RESULTS: Previously vaccinated participants manifested secondary antibody responses after receipt of low-dose Anhui vaccine ("boosting"); by day 28, 21% to 50% developed HAI responses of 1:40 or greater. Use of adjuvant was not associated with increased HAI responses. Among vaccine-naive participants (n = 565), the optimum dose was 7.5 µg of antigen with adjuvant (geometric mean titer [GMT], 63.3; 95% CI, 43.0-93.1). The greatest response to unadjuvanted antigen was seen at the highest dose, 90 µg (GMT, 28.5; 95% CI, 19.7-41.2). Local or systemic reactions occurred, respectively, in 40 (78%) and 25 (49%) of 51 participants who received 7.5 µg plus adjuvant vs 50 (88%) and 29 (51%) of 57 who received 90 µg of unadjuvanted vaccine. In general, antibodies were short-lived, and by day 180, HAI titers had decreased to less than 1:20 in all treatment groups. CONCLUSIONS AND RELEVANCE: Previous receipt of a single dose of influenza A(H5N1) Vietnam vaccine was associated with sufficient immunologic priming to facilitate antibody response to a different H5N1 antigen using low-dose Anhui (booster) vaccine. In participants who had not previously received H5 vaccine, low-dose Anhui vaccine plus adjuvant was more immunogenic compared with higher doses of unadjuvanted vaccine. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00680069.

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

October 8, 2014

Volume

312

Issue

14

Start / End Page

1420 / 1428

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Squalene
  • Polysorbates
  • Middle Aged
  • Male
  • Influenza, Human
  • Influenza Vaccines
  • Influenza A Virus, H5N1 Subtype
  • Immunization, Secondary
 

Citation

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Belshe, R. B., Frey, S. E., Graham, I. L., Anderson, E. L., Jackson, L. A., Spearman, P., … National Institute of Allergy and Infectious Diseases–Funded Vaccine and Treatment Evaluation Units, . (2014). Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial. JAMA, 312(14), 1420–1428. https://doi.org/10.1001/jama.2014.12609
Belshe, Robert B., Sharon E. Frey, Irene L. Graham, Edwin L. Anderson, Lisa A. Jackson, Paul Spearman, Srilatha Edupuganti, et al. “Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial.JAMA 312, no. 14 (October 8, 2014): 1420–28. https://doi.org/10.1001/jama.2014.12609.
Belshe RB, Frey SE, Graham IL, Anderson EL, Jackson LA, Spearman P, et al. Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial. JAMA. 2014 Oct 8;312(14):1420–8.
Belshe, Robert B., et al. “Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial.JAMA, vol. 312, no. 14, Oct. 2014, pp. 1420–28. Pubmed, doi:10.1001/jama.2014.12609.
Belshe RB, Frey SE, Graham IL, Anderson EL, Jackson LA, Spearman P, Edupuganti S, Mulligan MJ, Rouphael N, Winokur P, Dolor RJ, Woods CW, Walter EB, Chen WH, Turley C, Edwards KM, Creech CB, Hill H, Bellamy AR, National Institute of Allergy and Infectious Diseases–Funded Vaccine and Treatment Evaluation Units. Immunogenicity of avian influenza A/Anhui/01/2005(H5N1) vaccine with MF59 adjuvant: a randomized clinical trial. JAMA. 2014 Oct 8;312(14):1420–1428.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

October 8, 2014

Volume

312

Issue

14

Start / End Page

1420 / 1428

Location

United States

Related Subject Headings

  • Young Adult
  • Vaccination
  • Squalene
  • Polysorbates
  • Middle Aged
  • Male
  • Influenza, Human
  • Influenza Vaccines
  • Influenza A Virus, H5N1 Subtype
  • Immunization, Secondary