Giuseppe
Emeritus
Vaccine. 2009 Apr 27. [Epub ahead of print]
Single- and multiple-clade influenza A H5N1 vaccines induce cross protection in ferrets.
Forrest HL, Khalenkov AM, Govorkova EA, Kim JK, Del Giudice G, Webster RG. - Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
The rapid evolution, genetic diversity, broad host range, and increasing human infection with avian influenza A (H5N1) viruses highlight the need for an efficacious cross-clade vaccine.
Using the ferret model, we compared induction of cross-reactive immunity and protective efficacy of three single-clade H5N1 vaccines and a novel multiple-clade H5N1 vaccine, with and without MF59 adjuvant.
Reverse genetics (rg) was used to generate vaccine viruses containing the hemagglutinin (HA) and neuraminidase genes of wild-type H5N1 viruses. Ferrets received 2 doses of inactivated whole-virus vaccine separated by 3 weeks.
Single-clade vaccines (7.5mug HA per dose) included rg-A/Vietnam/1203/04 (clade 1), rg-A/Hong Kong/213/03 (clade 1), and rg-A/Japanese white eye/Hong Kong/1038/06 (clade 2.3). The multiple-clade vaccine contained 3.75mug HA per dose of each single-clade vaccine and of rg-A/Whooper Swan/Mongolia/244/05 (clade 2.2).
Two doses of vaccine were required to substantially increase anti-HA and virus neutralizing antibody titers to H5N1 viruses.
MF59 adjuvant enhanced induction of clade-specific and cross-clade serum antibody responses, reduced frequency of infection (as determined by upper respiratory tract virus shedding and seroconversion data), and eliminated disease signs.
The rg-A/Hong Kong/213/03 vaccine induced the highest antibody titers to homologous and heterologous H5N1 viruses, while rg-A/Japanese white eye/Hong Kong/1038/06 vaccine induced the lowest. The multiple-clade vaccine was broadly immunogenic against clade 1 and 2 viruses.
The rg-A/Vietnam/1203/04 vaccine (the currently stockpiled H5N1 vaccine) most effectively reduced upper respiratory tract virus shedding after challenge with clade 1 and 2 viruses.
Importantly, all vaccines protected against lethal challenge with A/Vietnam/1203/04 virus and provided cross-clade protection.
PMID: 19406182 [PubMed - as supplied by publisher]
-
------
Single- and multiple-clade influenza A H5N1 vaccines induce cross protection in ferrets.
Forrest HL, Khalenkov AM, Govorkova EA, Kim JK, Del Giudice G, Webster RG. - Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
The rapid evolution, genetic diversity, broad host range, and increasing human infection with avian influenza A (H5N1) viruses highlight the need for an efficacious cross-clade vaccine.
Using the ferret model, we compared induction of cross-reactive immunity and protective efficacy of three single-clade H5N1 vaccines and a novel multiple-clade H5N1 vaccine, with and without MF59 adjuvant.
Reverse genetics (rg) was used to generate vaccine viruses containing the hemagglutinin (HA) and neuraminidase genes of wild-type H5N1 viruses. Ferrets received 2 doses of inactivated whole-virus vaccine separated by 3 weeks.
Single-clade vaccines (7.5mug HA per dose) included rg-A/Vietnam/1203/04 (clade 1), rg-A/Hong Kong/213/03 (clade 1), and rg-A/Japanese white eye/Hong Kong/1038/06 (clade 2.3). The multiple-clade vaccine contained 3.75mug HA per dose of each single-clade vaccine and of rg-A/Whooper Swan/Mongolia/244/05 (clade 2.2).
Two doses of vaccine were required to substantially increase anti-HA and virus neutralizing antibody titers to H5N1 viruses.
MF59 adjuvant enhanced induction of clade-specific and cross-clade serum antibody responses, reduced frequency of infection (as determined by upper respiratory tract virus shedding and seroconversion data), and eliminated disease signs.
The rg-A/Hong Kong/213/03 vaccine induced the highest antibody titers to homologous and heterologous H5N1 viruses, while rg-A/Japanese white eye/Hong Kong/1038/06 vaccine induced the lowest. The multiple-clade vaccine was broadly immunogenic against clade 1 and 2 viruses.
The rg-A/Vietnam/1203/04 vaccine (the currently stockpiled H5N1 vaccine) most effectively reduced upper respiratory tract virus shedding after challenge with clade 1 and 2 viruses.
Importantly, all vaccines protected against lethal challenge with A/Vietnam/1203/04 virus and provided cross-clade protection.
PMID: 19406182 [PubMed - as supplied by publisher]
-
------
