Induction of long-term protective immune responses by influenza H5N1 virus-like particles.
BACKGROUND
Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.


RESULTS
Influenza virus-like particles (VLPs) produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1) hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.


CONCLUSIONS
These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.
Kang
Sang-Moo
SM
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA. skang2@emory.edu
Yoo
Dae-Goon
DG
Lipatov
Aleksandr S
AS
Song
Jae-Min
JM
Davis
C Todd
CT
Quan
Fu-Shi
FS
Chen
Li-Mei
LM
Donis
Ruben O
RO
Compans
Richard W
RW
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers; D005260:Female; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014771:Virion / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D017931:DNA Primers