H5N1 Whole-Virus Vaccine Induces Neutralizing Antibodies in Humans Which Are Protective in a Mouse Passive Transfer Model

被引:16
作者
Howard, M. Keith [1 ]
Sabarth, Nicolas [1 ]
Savidis-Dacho, Helga [1 ]
Portsmouth, Daniel [1 ]
Kistner, Otfried [1 ]
Kreil, Thomas R. [1 ]
Ehrlich, Hartmut J. [2 ]
Barrett, P. Noel [1 ]
机构
[1] Baxter BioSci, Vaccine Res & Dev, Orth, Austria
[2] Baxter BioSci, Global Res & Dev, Vienna, Austria
来源
PLOS ONE | 2011年 / 6卷 / 08期
关键词
PANDEMIC INFLUENZA VACCINE; CELL-CULTURE; MONOCLONAL-ANTIBODIES; THERAPEUTIC-EFFICACY; EGG-ADAPTATION; H1N1; VACCINE; WILD-TYPE; INFECTION; MICE; HEMAGGLUTININ;
D O I
10.1371/journal.pone.0023791
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; however, clinical efficacy is difficult to evaluate in the absence of wide-spread human disease. A lethal mouse model has been utilized which allows investigation of the protective efficacy of active vaccination or passive transfer of vaccine induced sera following lethal H5N1 challenge. Methods: We used passive transfer of immune sera to investigate antibody-mediated protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole-virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced rodent or human immune sera and subsequently challenged with a lethal dose of wild-type H5N1 virus. Results: Passive transfer of H5N1 vaccine-induced mouse, guinea pig and human immune sera provided dose-dependent protection of recipient mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty values for serum H5N1 neutralizing antibody titers were calculated to be <= 1:11 for all immune sera, independently of source species. Conclusions: These data underpin the confidence that the Vero cell culture-derived, whole-virus H5N1 vaccine will be effective in a pandemic situation and support the use of neutralizing serum antibody titers as a correlate of protection for H5N1 vaccines.
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