• Vaccine · May 2009

    Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets.

    • Min-Suk Song, Taek-Kyu Oh, Philippe Noriel Q Pascua, Ho-Jin Moon, Jun Han Lee, Yun Hee Baek, Kyu-Jin Woo, Yeup Yoon, Moon-Hee Sung, Haryoung Poo, Chul-Joong Kim, and Young Ki Choi.
    • College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
    • Vaccine. 2009 May 21; 27 (24): 3145-52.

    AbstractTo 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 (RgKoreaW149/06 x PR8) 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 15microg of HA) elicited high HI titers in a dose-dependent manner. Mice immunized with RgKoreaW149/06 x PR8 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 1.77microg while all immunized ferrets were completely protected. Two-dose (7.5microg) vaccinated mice (HI titer > or =320) and triple dose (7.5 microg) vaccinated ferrets with RgKoreaES223N/03xPR8 (HI titer > or =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 (> or =640 HI titer) for full protection of the vaccinated hosts that could provide a preliminary basis for the assessment of complete immunization.

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