tetano
Editor, Senior Moderator
Vaccine. 2018 Nov 27. pii: S0264-410X(18)31589-5. doi: 10.1016/j.vaccine.2018.11.064. [Epub ahead of print]
[h=1]Preclinical evaluation of the efficacy of an H5N8 vaccine candidate (IDCDC-RG43A) in mouse and ferret models for pandemic preparedness.[/h] Jeong JH[SUP]1[/SUP], Kim EH[SUP]1[/SUP], Lloren KKS[SUP]1[/SUP], Kwon JJ[SUP]1[/SUP], Kwon HI[SUP]1[/SUP], Ahn SJ[SUP]1[/SUP], Kim YI[SUP]1[/SUP], Choi WS[SUP]1[/SUP], Si YJ[SUP]1[/SUP], Lee OJ[SUP]1[/SUP], Han HJ[SUP]2[/SUP], Baek YH[SUP]1[/SUP], Song MS[SUP]3[/SUP], Choi YK[SUP]4[/SUP], Kim CJ[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra-clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 ?g/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus.
[h=4]KEYWORDS:[/h] H5N8 pre-pandemic vaccine; Immunogenicity; Preclinical evaluation; Protective efficacy
PMID: 30502069 DOI: 10.1016/j.vaccine.2018.11.064
[h=1]Preclinical evaluation of the efficacy of an H5N8 vaccine candidate (IDCDC-RG43A) in mouse and ferret models for pandemic preparedness.[/h] Jeong JH[SUP]1[/SUP], Kim EH[SUP]1[/SUP], Lloren KKS[SUP]1[/SUP], Kwon JJ[SUP]1[/SUP], Kwon HI[SUP]1[/SUP], Ahn SJ[SUP]1[/SUP], Kim YI[SUP]1[/SUP], Choi WS[SUP]1[/SUP], Si YJ[SUP]1[/SUP], Lee OJ[SUP]1[/SUP], Han HJ[SUP]2[/SUP], Baek YH[SUP]1[/SUP], Song MS[SUP]3[/SUP], Choi YK[SUP]4[/SUP], Kim CJ[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra-clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 ?g/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus.
[h=4]KEYWORDS:[/h] H5N8 pre-pandemic vaccine; Immunogenicity; Preclinical evaluation; Protective efficacy
PMID: 30502069 DOI: 10.1016/j.vaccine.2018.11.064