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Vaccine. 2009 May 21;27(24):3145-52. Epub 2009 Apr 9.
Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets.
Song MS, Oh TK, Pascua PN, Moon HJ, Lee JH, Baek YH, Woo KJ, Yoon Y, Sung MH, Poo H, Kim CJ, Choi YK. College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong, Heungduk-Ku, Cheongju 361-763, Republic of Korea.
To investigate the biological indicator for vaccine efficacy against HPAI H5N1 virus challenge of varying clades, two inactivated whole-virus H5N1 vaccines containing the hemagglutinin (HA) and neuraminidase (NA) genes of either clade 2.2 A/EM/Korea/W149/06 (RgKoreaW149/06xPR8) or clade 2.5 A/Ck/Korea/ES/03 (RgKoreaES223N/03XPR8) virus in the background of A/PR/8/34 (H1N1) were generated by reverse genetics.
Administration of the vaccines (2-dose 1.77, 3.5, 7.5 or 15mug of HA) elicited high HI titers in a dose-dependent manner. Mice immunized with RgKoreaW149/06xPR8 were completely protected from challenge against wild-type A/EM/Korea/W149/06 without clinical signs of infection.
RgKoreaES223N/03XPR8 could not protect mice at 1.77mug while all immunized ferrets were completely protected. Two-dose (7.5mug) vaccinated mice (HI titer >/=320) and triple dose (7.5mug) vaccinated ferrets with RgKoreaES223N/03xPR8 (HI titer >/=640) protected vaccine recipients from mortality, inhibited nasal virus shedding and limited influenza virus tropism.
Thus, these vaccines provided cross-protectivity in both models. More importantly, these results collectively suggested a positive correlation between vaccine-induced HI titers and inhibition of virus shedding including block of viral proliferation in major organs against a heterologous HPAI H5N1 virus.
Although developing technologies or methods that will enable the reduction of administration dose/frequency remains to be resolved, our study demonstrated a considerable biological marker (>/=640 HI titer) for full protection of the vaccinated hosts that could provide a preliminary basis for the assessment of complete immunization.
PMID: 19446184 [PubMed - in process]
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Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets.
Song MS, Oh TK, Pascua PN, Moon HJ, Lee JH, Baek YH, Woo KJ, Yoon Y, Sung MH, Poo H, Kim CJ, Choi YK. College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong, Heungduk-Ku, Cheongju 361-763, Republic of Korea.
To investigate the biological indicator for vaccine efficacy against HPAI H5N1 virus challenge of varying clades, two inactivated whole-virus H5N1 vaccines containing the hemagglutinin (HA) and neuraminidase (NA) genes of either clade 2.2 A/EM/Korea/W149/06 (RgKoreaW149/06xPR8) or clade 2.5 A/Ck/Korea/ES/03 (RgKoreaES223N/03XPR8) virus in the background of A/PR/8/34 (H1N1) were generated by reverse genetics.
Administration of the vaccines (2-dose 1.77, 3.5, 7.5 or 15mug of HA) elicited high HI titers in a dose-dependent manner. Mice immunized with RgKoreaW149/06xPR8 were completely protected from challenge against wild-type A/EM/Korea/W149/06 without clinical signs of infection.
RgKoreaES223N/03XPR8 could not protect mice at 1.77mug while all immunized ferrets were completely protected. Two-dose (7.5mug) vaccinated mice (HI titer >/=320) and triple dose (7.5mug) vaccinated ferrets with RgKoreaES223N/03xPR8 (HI titer >/=640) protected vaccine recipients from mortality, inhibited nasal virus shedding and limited influenza virus tropism.
Thus, these vaccines provided cross-protectivity in both models. More importantly, these results collectively suggested a positive correlation between vaccine-induced HI titers and inhibition of virus shedding including block of viral proliferation in major organs against a heterologous HPAI H5N1 virus.
Although developing technologies or methods that will enable the reduction of administration dose/frequency remains to be resolved, our study demonstrated a considerable biological marker (>/=640 HI titer) for full protection of the vaccinated hosts that could provide a preliminary basis for the assessment of complete immunization.
PMID: 19446184 [PubMed - in process]
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