An adjuvanted, low-dose, pandemic influenza a (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults

作者：Levie Karin^*; Leroux Roels Isabel; Hoppenbrouwers Karel; Kervyn Anne Diane; Vandermeulen Corinne; Forgus Sheron; Leroux Roels Geert; Pichon Sylvie; Kusters Inca

来源：Journal of Infectious Diseases, 2008, 198(5): 642-649.

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 mu g of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 mu g 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 mu g 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-mu g 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.

• 出版日期2008-9-1