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Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial

(2007) LANCET. 370(9587). p.580-589
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Abstract
Background Antigen sparing is regarded as crucial for pandemic vaccine development because worldwide influenza vaccine production capacity is limited. Adjuvantation is an important antigen-sparing strategy. We assessed the safety and immunogenicity of a recombinant H5N1 split-virion vaccine formulated with a proprietary adjuvant system and investigated whether it can induce cross-reactive immunity. Methods Two doses of an inactivated split A/Vietnam/1194/2004 NIBRG-14 (recombinant H5N1 engineered by reverse genetics) vaccine were administered 21 days apart to eight groups of 50 volunteers aged 18-60 years. We studied four antigen doses (3.8 mu g, 7.5 mu g, 15 mu g, and 30 mu g haemagglutinin) given with or without adjuvant. Blood samples were collected to analyse humoral immune response. Adverse events were recorded up through study day 51. Safety analyses were of the whole vaccinated cohort and immunogenicity analyses per protocol. This trial is registered with the ClinicalTrials.gov, number NCT00309634. Findings All eight vaccine formulations had a good safety profile. No serious adverse events were reported. The adjuvanted vaccines induced more injection-site symptoms and general symptoms than did the non-adjuvanted vaccines, but most were mild to moderate in intensity and transient in nature. The adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all antigen doses. At the lowest antigenic dose (3.8 mu g), immune responses for the adjuvanted vaccine against the recombinant homologous vaccine strain (A/Vietnam/1194/2004 NIBRG-14, clade 1) met or exceeded all US Food and Drug Administration and European Union licensure criteria. Furthermore, 37 of 48 (77%) participants receiving 3.8 mu g of the adjuvanted vaccine seroconverted for neutralising antibodies against a strain derived by reverse genetics from a drifted H5N1 isolate (A/Indonesia/5/2005, clade 2). Interpretation Adjuvantation conferred significant antigen sparing that could increase the production capacity of pandemic influenza vaccine. Moreover, the cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed for immunisation before a pandemic.
Keywords
SAFETY, HEMAGGLUTININ, IMMUNOGENICITY, OLD MICE, MF59-ADJUVANTED INFLUENZA, A H5N1 VIRUS, AVIAN INFLUENZA, PREPAREDNESS, STRATEGIES, ANTIBODY

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Chicago
Leroux-Roels, Isabel, Astrid Borkowski, THOMAS VANWOLLEGHEM, Mamadou Drame, Frédéric Clement, Eliane Hons, Jeanne-Marie Devaster, and Geert Leroux-Roels. 2007. “Antigen Sparing and Cross-reactive Immunity with an Adjuvanted rH5N1 Prototype Pandemic Influenza Vaccine: a Randomised Controlled Trial.” Lancet 370 (9587): 580–589.
APA
Leroux-Roels, I., Borkowski, A., VANWOLLEGHEM, T., Drame, M., Clement, F., Hons, E., Devaster, J.-M., et al. (2007). Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. LANCET, 370(9587), 580–589.
Vancouver
1.
Leroux-Roels I, Borkowski A, VANWOLLEGHEM T, Drame M, Clement F, Hons E, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. LANCET. 2007;370(9587):580–9.
MLA
Leroux-Roels, Isabel, Astrid Borkowski, THOMAS VANWOLLEGHEM, et al. “Antigen Sparing and Cross-reactive Immunity with an Adjuvanted rH5N1 Prototype Pandemic Influenza Vaccine: a Randomised Controlled Trial.” LANCET 370.9587 (2007): 580–589. Print.
@article{426775,
  abstract     = {Background Antigen sparing is regarded as crucial for pandemic vaccine development because worldwide influenza vaccine production capacity is limited. Adjuvantation is an important antigen-sparing strategy. We assessed the safety and immunogenicity of a recombinant H5N1 split-virion vaccine formulated with a proprietary adjuvant system and investigated whether it can induce cross-reactive immunity. 
Methods Two doses of an inactivated split A/Vietnam/1194/2004 NIBRG-14 (recombinant H5N1 engineered by reverse genetics) vaccine were administered 21 days apart to eight groups of 50 volunteers aged 18-60 years. We studied four antigen doses (3.8 mu g, 7.5 mu g, 15 mu g, and 30 mu g haemagglutinin) given with or without adjuvant. Blood samples were collected to analyse humoral immune response. Adverse events were recorded up through study day 51. Safety analyses were of the whole vaccinated cohort and immunogenicity analyses per protocol. This trial is registered with the ClinicalTrials.gov, number NCT00309634. 
Findings All eight vaccine formulations had a good safety profile. No serious adverse events were reported. The adjuvanted vaccines induced more injection-site symptoms and general symptoms than did the non-adjuvanted vaccines, but most were mild to moderate in intensity and transient in nature. The adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all antigen doses. At the lowest antigenic dose (3.8 mu g), immune responses for the adjuvanted vaccine against the recombinant homologous vaccine strain (A/Vietnam/1194/2004 NIBRG-14, clade 1) met or exceeded all US Food and Drug Administration and European Union licensure criteria. Furthermore, 37 of 48 (77%) participants receiving 3.8 mu g of the adjuvanted vaccine seroconverted for neutralising antibodies against a strain derived by reverse genetics from a drifted H5N1 isolate (A/Indonesia/5/2005, clade 2). 
Interpretation Adjuvantation conferred significant antigen sparing that could increase the production capacity of pandemic influenza vaccine. Moreover, the cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed for immunisation before a pandemic.},
  author       = {Leroux-Roels, Isabel and Borkowski, Astrid and VANWOLLEGHEM, THOMAS and Drame, Mamadou and Clement, Frédéric and Hons, Eliane and Devaster, Jeanne-Marie and Leroux-Roels, Geert},
  issn         = {0140-6736},
  journal      = {LANCET},
  keywords     = {SAFETY,HEMAGGLUTININ,IMMUNOGENICITY,OLD MICE,MF59-ADJUVANTED INFLUENZA,A H5N1 VIRUS,AVIAN INFLUENZA,PREPAREDNESS,STRATEGIES,ANTIBODY},
  language     = {eng},
  number       = {9587},
  pages        = {580--589},
  title        = {Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial},
  url          = {http://dx.doi.org/10.1016/S0140-6736(07)61297-5},
  volume       = {370},
  year         = {2007},
}

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