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

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Title
Investigation of the biological indicator for vaccine efficacy against highly pathogenic avian influenza (HPAI) H5N1 virus challenge in mice and ferrets
Author(s)
M S Song; T K Oh; P N Q Pascua; H J Moon; J H Lee; Y H Baek; K J Woo; Y Yoon; M H Sung; Haryoung Poo; C J Kim; Y K Choi
Bibliographic Citation
Vaccine, vol. 27, no. 24, pp. 3145-3152
Publication Year
2009
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 15μg 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 1.77μg while all immunized ferrets were completely protected. Two-dose (7.5μg) vaccinated mice (HI titer ≥320) and triple dose (7.5μg) 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.
Keyword
HPAI H5N1vaccinebiological markercross-protection
ISSN
0264-410X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.vaccine.2009.03.061
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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