Protective immunity against H5N1 influenza virus by a single dose vaccination with virus-like particles.
We generated influenza virus-like particles (VLPs) containing the wild type (WT) H5 hemagglutinin (HA) from A/Viet Nam/1203/04 virus or a mutant H5 HA with a deletion of the multibasic cleavage motif. VLPs containing mutant H5 HA were found to be as immunogenic as VLPs containing WT HA. A single intramuscular vaccination with either type of H5 VLPs provided complete protection against lethal challenge. In contrast, the recombinant H5 HA vaccine was less immunogenic and vaccination even with a 5 fold higher dose did not induce protective immunity. VLP vaccines were superior to the recombinant HA in inducing T helper type 1 immune responses, hemagglutination inhibition titers, and antibody secreting cells, which significantly contribute to inducing protective immunity after a single dose vaccination. This study provides insights into the potential mechanisms of improved immunogenicity by H5 VLP vaccines as an approach to improve the protective efficacy against potential pandemic viruses.
Song
Jae-Min
JM
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, Atlanta, Georgia, USA.
Hossain
Jaber
J
Yoo
Dae-Goon
DG
Lipatov
Aleksandr S
AS
Davis
C Todd
CT
Quan
Fu-Shi
FS
Chen
Li-Mei
LM
Hogan
Robert J
RJ
Donis
Ruben O
RO
Compans
Richard W
RW
Kang
Sang-Moo
SM
D000818:Animals; D000914:Antibodies, Viral; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D004334:Drug Administration Schedule; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D013154:Spleen / Q000166:cytology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines