Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine

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• 作者：Paul A. Tambyah^a ; Annelies Wilder-Smith^a ; Borislava G. Pavlova^b ; P. Noel Barrett^b ; Helen M.L. Oh^c ; David S. Hui^d ; Kwok-yung Yuen^e ; Sandor Fritsch^b ; Gerald Aichinger^b ; Alexandra Loew-Baselli^b ; Maikel van der Velden^b ; Friedrich Maritsch^b ; Otfried Kistner^b ; Hartmut J. Ehrlich^b ; ^{hartmut_ehrlich@baxter.com}
• 关键词：Avian influenza ; H5N1 ; Pre-pandemic vaccine ; Pandemic vaccine ; Immunogenicity ; Safety ; PHASE I/II
• 刊名：Vaccine
• 出版年：2012
• 出版时间：5 January 2012
• 年：2012
• 卷：30
• 期：2
• 页码：329-335
• 全文大小：252 K

文摘

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-na?ve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N = 110) were randomized 1:1 to receive two vaccinations with either 3.75 ¦Ìg or 7.5 ¦Ìg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14 % which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ?#xA0;1:20) against the vaccine strain A/Indonesia/05/2005: 82.7 % and 86.5 % in the 3.75 ¦Ìg and 7.5 ¦Ìg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40 % and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 ¦Ìg dose group determined by SRH was only marginally lower (69.2 % ) than the CPMP criterion of >70 % . Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21 % by MN and ?5 % by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.