Giuseppe
Emeritus
[Presented in part: Bangkok International Conference on Avian Influenza 2008: Integration from Knowledge to Control, Bangkok, 23-25 January 2008.]
[ABSTRACTS, RESEARCH] An Adjuvanted, Low-Dose, Pandemic Influenza A (H5N1) Vaccine Candidate Is Safe, Immunogenic, and Induces Cross-Reactive Immune Responses in Healthy Adults
Karin Levie,1 Isabel Leroux-Roels,2 Karel Hoppenbrouwers,3 Anne-Diane Kervyn,1 Corinne Vandermeulen,3 Sheron Forgus,2 Geert Leroux-Roels,2 Sylvie Pichon,4 and Inca Kusters4
1Ecole de Sant? Publique, Universit? Catholique de Louvain, Brussels, 2Center for Vaccinology, Ghent University and Hospital, Ghent, and 3Centre for Youth Health Care, Katholieke Universiteit, Leuven, Belgium; 4Sanofi Pasteur, Marcy l'Etoile, France
Background.
To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity.
Methods.
In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 μg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 μg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination.
Results.
No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 μg of hemagglutinin plus adjuvant, 72% of subjects had HI titers 1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant.
Conclusions.
The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-μg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine.
Trial registration. ClinicalTrials.gov identifier: NCT00457509.
Received 12 February 2008; accepted 28 April 2008; electronically published 24 June 2008.
Potential conflicts of interest: K.L., K.H., and G.L.-R. have been principal investigators of vaccine trials for several vaccine manufacturers, including Sanofi Pasteur, for which their institutions obtained research grants. S.P. and I.K. are employed by Sanofi Pasteur. All other authors declare no potential conflicts.
Presented in part: Bangkok International Conference on Avian Influenza 2008: Integration from Knowledge to Control, Bangkok, 23-25 January 2008.
Financial support: Sanofi Pasteur, France.
(See the article by Goji et al., on pages XXX-XX, and the editorial commentary by Poland and Sambhara, on pages XXX-XX.)
Reprints or correspondence: Dr. Karin Levie, Ecole de Sant? Publique, UCL, Clos Chapelle aux Champs 30 B39, 1200 Brussels, Belgium (karin.levie@centredesante.ucl.ac.be).
-
------
[ABSTRACTS, RESEARCH] An Adjuvanted, Low-Dose, Pandemic Influenza A (H5N1) Vaccine Candidate Is Safe, Immunogenic, and Induces Cross-Reactive Immune Responses in Healthy Adults
Karin Levie,1 Isabel Leroux-Roels,2 Karel Hoppenbrouwers,3 Anne-Diane Kervyn,1 Corinne Vandermeulen,3 Sheron Forgus,2 Geert Leroux-Roels,2 Sylvie Pichon,4 and Inca Kusters4
1Ecole de Sant? Publique, Universit? Catholique de Louvain, Brussels, 2Center for Vaccinology, Ghent University and Hospital, Ghent, and 3Centre for Youth Health Care, Katholieke Universiteit, Leuven, Belgium; 4Sanofi Pasteur, Marcy l'Etoile, France
Background.
To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity.
Methods.
In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 μg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 μg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination.
Results.
No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 μg of hemagglutinin plus adjuvant, 72% of subjects had HI titers 1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant.
Conclusions.
The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-μg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine.
Trial registration. ClinicalTrials.gov identifier: NCT00457509.
Received 12 February 2008; accepted 28 April 2008; electronically published 24 June 2008.
Potential conflicts of interest: K.L., K.H., and G.L.-R. have been principal investigators of vaccine trials for several vaccine manufacturers, including Sanofi Pasteur, for which their institutions obtained research grants. S.P. and I.K. are employed by Sanofi Pasteur. All other authors declare no potential conflicts.
Presented in part: Bangkok International Conference on Avian Influenza 2008: Integration from Knowledge to Control, Bangkok, 23-25 January 2008.
Financial support: Sanofi Pasteur, France.
(See the article by Goji et al., on pages XXX-XX, and the editorial commentary by Poland and Sambhara, on pages XXX-XX.)
Reprints or correspondence: Dr. Karin Levie, Ecole de Sant? Publique, UCL, Clos Chapelle aux Champs 30 B39, 1200 Brussels, Belgium (karin.levie@centredesante.ucl.ac.be).
-
------
