An Adjuvanted, Low-Dose, Pandemic Influenza A (H5N1) Vaccine Candidate Is Safe, Immunogenic, and Induces Cross-Reactive Immune Responses in Healthy Adults

• Published in: The Journal of infectious diseases 2008-09, Vol.198 (5), p.642-649
• Main Authors: Levie, Karin, Leroux-Roels, Isabel, Hoppenbrouwers, Karel, Kervyn, Anne-Diane, Vandermeulen, Corinne, Forgus, Sheron, Leroux-Roels, Geert, Pichon, Sylvie, Kusters, Inca
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Adolescent; Adult; Antibodies; Antibodies, Viral - blood; Antigens; Cross Reactions; Dose-Response Relationship, Immunologic; Emulsions; Female; H5N1 subtype influenza A virus; Hemagglutination Inhibition Tests; Humans; Immune response; Influenza A virus; Influenza A Virus, H5N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Male; Pandemics; Single-Blind Method; Vaccination; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/590913

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.