Kinetics of immune responses to influenza virus-like particles and dose-dependence of protection with a single vaccination.
The format of influenza virus-like particles (VLPs) as a nonreplicating particulate vaccine candidate is a promising alternative to conventional egg-based vaccines. In this study, we have investigated the detailed kinetics of immune responses and protective efficacy after a single intranasal immunization with different doses of VLPs alone or in the presence of an Escherichia coli mutant heat-labile enterotoxin [mLT(R192G)] or cholera toxin subunit B as adjuvants. Analysis of immune responses showed differential kinetics in a VLP antigen dose-dependent manner and dynamic changes in the ratios of antibody immunoglobulin G isotypes over the time course. Protection against lethal challenge was observed with a single immunization with influenza VLPs even without adjuvant. The addition of adjuvant showed significant antigen-sparing effects with improved protective efficacy. The protective immune responses, efficacies of protection, and antigen-sparing effects were significantly improved by a second immunization as determined by the levels of neutralizing antibodies, morbidity postchallenge, lung viral titers, and inflammatory cytokines. Our results are informative for a better understanding of the protective immunity induced by a single dose or two doses of influenza VLPs, which is dependent on antigen dosage and the presence of adjuvant, and will provide insights into designing effective vaccines based on VLPs.
Quan
Fu Shi
FS
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Yoo
Dae-Goon
DG
Song
Jae-Min
JM
Clements
John D
JD
Compans
Richard W
RW
Kang
Sang-Moo
SM
D000818:Animals; D002460:Cell Line; D004285:Dogs; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D014771:Virion / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines