Giuseppe
Emeritus
Abstract. Immunogenicity, Safety, and Cross‐Reactivity of an Inactivated, Adjuvanted, Prototype Pandemic Influenza (H5N1) Vaccine: A Phase II, Double‐Blind, Randomized Trial.
Clinical Infectious Diseases 2009;48:000?000
? 2009 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2009/4808-00XX$15.00
DOI: 10.1086/597401
MAJOR ARTICLE
Immunogenicity, Safety, and Cross‐Reactivity of an Inactivated, Adjuvanted, Prototype Pandemic Influenza (H5N1) Vaccine: A Phase II, Double‐Blind, Randomized Trial
Jiang Wu,1,a - Han‐Hua Fang,2,a - Jiang‐Ting Chen,3 - Ji‐Chen Zhou,4Zi‐ - Jian Feng,5 - Chang‐Gui Li,2 - Yuan‐Zheng Qiu,3 - Yan Liu,3 - Min Lu,1 - Li‐Ying Liu,4 - Shan‐Shan Dong,3 - Qiang Gao,3 - Xiao‐Mei Zhang,3 - Nan Wang,3 - Wei‐Dong Yin,3 and Xiao‐Ping Dong6
1 Beijing Centers for Diseases Control and Prevention,
2 National Institute for the Control of Pharmaceuticals and Biological Products,
3 Sinovac Biotech,
4 Huairou Center for Disease Control and Prevention,
5 Chinese Center for Disease Control and Prevention, and
6 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Background.
Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole‐virion vaccines are regarded as antigen sparing for pandemic vaccines.
Methods.
A double‐blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum‐adjuvanted, whole‐virion H5N1 vaccine containing 5, 10, or 15 μg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 μg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays.
Results.
All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 μg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10‐ and 15‐μg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross‐reaction assays showed that after 2 doses of 10 μg of vaccine, 98% and 87% of participants had a microneutralization titer of 1:40 against heterologous Indonesia and Anhui strains, respectively.
Conclusions.
The inactivated, aluminum‐adjuvanted, whole‐virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross‐reactivity against heterologous H5N1 strains in clade 2.
Trial registration.
ClinicalTrials.gov identifier: NCT00535665.
Received 14 October 2008; accepted 16 December 2008; electronically published 12 March 2009.
Reprints or correspondence: Dr. Xiao‐Ping Dong, Ying‐Xin Rd. 100, Beijing (100052), People's Republic of China (dongxp238@sina.com); or Dr. Wei‐Dong Yin, No.39 Shangdi Western Road, Haidian District, Beijing (100085), People?s Republic of China (yinweidong@sinovac.com).
* aJ.W. and H.‐H.F. contributed equally to the work.
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<cite cite="http://www.journals.uchicago.edu/doi/abs/10.1086/597401">Chicago Journals - Clinical Infectious Diseases</cite>? 2009 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2009/4808-00XX$15.00
DOI: 10.1086/597401
MAJOR ARTICLE
Immunogenicity, Safety, and Cross‐Reactivity of an Inactivated, Adjuvanted, Prototype Pandemic Influenza (H5N1) Vaccine: A Phase II, Double‐Blind, Randomized Trial
Jiang Wu,1,a - Han‐Hua Fang,2,a - Jiang‐Ting Chen,3 - Ji‐Chen Zhou,4Zi‐ - Jian Feng,5 - Chang‐Gui Li,2 - Yuan‐Zheng Qiu,3 - Yan Liu,3 - Min Lu,1 - Li‐Ying Liu,4 - Shan‐Shan Dong,3 - Qiang Gao,3 - Xiao‐Mei Zhang,3 - Nan Wang,3 - Wei‐Dong Yin,3 and Xiao‐Ping Dong6
1 Beijing Centers for Diseases Control and Prevention,
2 National Institute for the Control of Pharmaceuticals and Biological Products,
3 Sinovac Biotech,
4 Huairou Center for Disease Control and Prevention,
5 Chinese Center for Disease Control and Prevention, and
6 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Background.
Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole‐virion vaccines are regarded as antigen sparing for pandemic vaccines.
Methods.
A double‐blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum‐adjuvanted, whole‐virion H5N1 vaccine containing 5, 10, or 15 μg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 μg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays.
Results.
All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 μg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10‐ and 15‐μg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross‐reaction assays showed that after 2 doses of 10 μg of vaccine, 98% and 87% of participants had a microneutralization titer of 1:40 against heterologous Indonesia and Anhui strains, respectively.
Conclusions.
The inactivated, aluminum‐adjuvanted, whole‐virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross‐reactivity against heterologous H5N1 strains in clade 2.
Trial registration.
ClinicalTrials.gov identifier: NCT00535665.
Received 14 October 2008; accepted 16 December 2008; electronically published 12 March 2009.
Reprints or correspondence: Dr. Xiao‐Ping Dong, Ying‐Xin Rd. 100, Beijing (100052), People's Republic of China (dongxp238@sina.com); or Dr. Wei‐Dong Yin, No.39 Shangdi Western Road, Haidian District, Beijing (100085), People?s Republic of China (yinweidong@sinovac.com).
* aJ.W. and H.‐H.F. contributed equally to the work.
-