Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

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• 作者：Hartmut J. Ehrlich^a ; ^{hartmut_ehrlich@baxter.com} ; Markus Mü ; ller^b ; Herwig Kollaritsch^c ; Fritz Pinl^d ; Bernhard Schmitt^e ; Markus Zeitlinger^b ; Alexandra Loew-Baselli^f ; Thomas R. Kreil^g ; Otfried Kistner^g ; Daniel Portsmouth^g ; Sandor Fritsch^a ; Friedrich Maritsch^a ; Gerald Aichinger^f ; Borislava G. Pavlova^a ; P. Noel Barrett^g
• 关键词：Influenza ; Vaccine ; H1N1 ; Pandemic ; Vero
• 刊名：Vaccine
• 出版年：2012
• 出版时间：22 June, 2012
• 年：2012
• 卷：30
• 期：30
• 页码：4543-4551
• 全文大小：394 K

文摘

Background

Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods

An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 ¦Ìg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.

Results

A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 ¦Ìg dose induced seroprotection rates of 86.9 % in adults and 75.2 % in elderly subjects. Two 7.5 ¦Ìg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9 % and 89.1 % , respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ? months post-vaccination. Between 34 % and 49 % of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008-09 or 2009-10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000-01 to 2006-07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55 % of tested sera. The vaccine was well tolerated with low rates of fever.

Conclusions

A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.