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

@article{citeulike:4548850, abstract = {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 15 μg 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 1.77 μg while all immunized ferrets were completely protected. Two-dose (7.5 μg) vaccinated mice (HI titer ≥320) and triple dose (7.5 μg) 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.}, author = {Song, Min-Suk and Oh, Taek-Kyu and Pascua, Philippe N. and Moon, Ho-Jin and Lee, Jun H. and Baek, Yun H. and Woo, Kyu-Jin and Yoon, Yeup and Sung, Moon-Hee and Poo, Haryoung}, citeulike-article-id = {4548850}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.vaccine.2009.03.061}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0264410X09004861}, day = {21}, doi = {10.1016/j.vaccine.2009.03.061}, issn = {0264410X}, journal = {Vaccine}, keywords = {influenza}, month = {May}, number = {24}, pages = {3145--3152}, posted-at = {2009-05-20 03:27:43}, priority = {2}, title = {Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets}, url = {http://dx.doi.org/10.1016/j.vaccine.2009.03.061}, volume = {27}, year = {2009} }

TY - JOUR ID - citeulike:4548850 L3 - citeulike-article-id:4548850 N2 - 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 15 μg 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 1.77 μg while all immunized ferrets were completely protected. Two-dose (7.5 μg) vaccinated mice (HI titer ≥320) and triple dose (7.5 μg) 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. IS - 24 JF - Vaccine SN - 0264410X EP - 3152 TI - Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets VL - 27 SP - 3145 KW - influenza AU - Song, Min-Suk AU - Oh, Taek-Kyu AU - Pascua, Philippe AU - Moon, Ho-Jin AU - Lee, Jun AU - Baek, Yun AU - Woo, Kyu-Jin AU - Yoon, Yeup AU - Sung, Moon-Hee AU - Poo, Haryoung PY - 2009/05/21/ UR - http://dx.doi.org/10.1016/j.vaccine.2009.03.061 ER -