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Journal of Virology, May 2009, p. 4489-4497, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02035-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinetics of Immune Responses to Influenza Virus-Like Particles and Dose-Dependence of Protection with a Single Vaccination{triangledown}

Fu Shi Quan,1 Dae-Goon Yoo,1 Jae-Min Song,1 John D. Clements,2 Richard W. Compans,1* and Sang-Moo Kang1*

Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322,1 Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, Louisiana 7011222

Received 26 September 2008/ Accepted 3 February 2009

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Phone for Richard W. Compans: (404) 727-5950. Fax: (404) 727-8250. E-mail: compans{at}microbio.emory.edu. Phone for Sang-Moo Kang: (404) 727-3228. Fax: (404) 727-3659. E-mail: skang2{at}emory.edu

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, May 2009, p. 4489-4497, Vol. 83, No. 9
0022-538X/09/$08.00+0     doi:10.1128/JVI.02035-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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