Abstract
BackgroundVero 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.MethodsWe 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.ResultsPassive 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.ConclusionsThese 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.
Highlights
Pathogenic avian influenza (HPAI) viruses of subtype A/ H5N1 continue to circulate in poultry and wild birds throughout Asia and Africa, causing sporadic human infections with a high case fatality rate
Our results demonstrate that a Vero cellderived, inactivated whole-virus H5N1 vaccine elicits potent humoral immune responses which following passive transfer protect mice against lethal challenge with wild-type H5N1 virus, and that protection correlates with serum neutralizing antibody titers
To evaluate the protective efficacy of immune sera elicited by a Vero cell culture-derived, whole-virus H5N1 vaccine, CD1 mice were passively immunized and subsequently challenged with a severe lethal dose of wild-type H5N1 virus
Summary
Pathogenic avian influenza (HPAI) viruses of subtype A/ H5N1 continue to circulate in poultry and wild birds throughout Asia and Africa, causing sporadic human infections with a high case fatality rate. Evaluation of candidate pandemic vaccines will enable manufacturers and regulatory authorities to answer critical questions regarding safety, immunogenicity and efficacy in advance of large-scale immunization programs. A number of H5N1 vaccines have been shown to be safe and immunogenic in clinical trials and to protect rodents and ferrets from lethal challenge with wild-type viruses (reviewed in [2]). Vero cell culture-derived whole-virus H5N1 vaccines have been extensively tested in clinical trials and consistently demonstrated to be safe and immunogenic; 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
