Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets.
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 (RgKoreaW149/06 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.
Song
Min-Suk
MS
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Oh
Taek-Kyu
TK
Pascua
Philippe Noriel Q
PN
Moon
Ho-Jin
HJ
Lee
Jun Han
JH
Baek
Yun Hee
YH
Woo
Kyu-Jin
KJ
Yoon
Yeup
Y
Sung
Moon-Hee
MH
Poo
Haryoung
H
Kim
Chul-Joong
CJ
Choi
Young Ki
YK
D000818:Animals; D015415:Biomarkers; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D014611:Vaccination
D015415:Biomarkers; D007252:Influenza Vaccines