Intranasal immunization with live attenuated influenza vaccine plus chitosan as an adjuvant protects mice against homologous and heterologous virus challenge.
ABSTRACT Our previous studies have proven the adjuvanticity of chitosan in mice when administered with inactivated and subunit influenza vaccine. In this study, we investigated the adjuvant effect of chitosan on the immunogenicity and protective efficacy of a live attenuated influenza vaccine. Mice were inoculated intranasally with live attenuated influenza vaccine plus chitosan and then challenged with a high, lethal dose of homologous or heterologous virus. Antibody responses, secretion of IFN-γ by spleen cells, body weight loss, survival rates, and residual lung virus titers were tested. The results demonstrated that live attenuated influenza vaccine with chitosan adjuvant not only protected mice completely against challenge with the homologous virus but also provided good cross-protection against a heterologous virus. In addition, chitosan as adjuvant could significantly increase the levels of antigen-specific antibodies and the population of IFN-γ-secreting T cells. These results reveal the potential of chitosan as a candidate adjuvant for use in a live attenuated influenza vaccine.
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ABSTRACT: Several global outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus have increased the urgency of developing effective and safe vaccines against H5N1. Compared with H5N1 inactivated vaccines used widely, H5N1 live-attenuated influenza vaccines (LAIVs) have advantages in vaccine efficacy, dose-saving formula, long-lasting effect, ease of administration and some cross-protective immunity. Furthermore, H5N1 LAIVs induce both humoral and cellular immune responses, especially including improved IgA production at the mucosa. The current trend of H5N1 LAIVs development is toward cold-adapted, temperature-sensitive or replication-defective vaccines, and moreover, H5N1 LAIVs plus mucosal adjuvants are promising candidates. This review provides an update on the advantages and development of H5N1 live-attenuated influenza vaccines.Viruses 12/2012; 4(12):3589-3605. DOI:10.3390/v4123589 · 3.28 Impact Factor
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ABSTRACT: PEGylation, including non-specific and site-directed ways, is a well-established and validated strategy to increase the stability, in vivo plasma retention time, and efficacy of protein pharmaceutics come together with the reduction of immunogenicity and hydrophobicity. Site-directed conjugation by PEG-aldehyde is the most widely used method for N-terminal modification, however, the generation of multi-modified products is inevitable due to lysine chemistry which always leads to difficulties in purification and quantification procedure. In this study, we developed a specific PEGylation strategy through the periodation of N-terminus of interferon beta-1b (IFN-β-1b) followed by the coupling of PEG-hydrazide. The prolonged elimination half-life and significantly diminished immunogenicity of PEG hydrazide-modified protein indicated an effective process in improving the properties of pharmacology and immunogenicity of IFN-β-1b. We further conducted comparisons on selectivity, velocity, yield and pharmacokinetics of the two methods. Results demonstrated that the hydrazide-based conjugation was a highly specific coupling reaction that only produced homogeneous N-terminal mono-PEGylated conjugate, while heterogeneous multi-modified products were generated in aldehyde-based process. In addition, fairly higher PEGylation yield was presented in the hydrazide conjugation compared with that of aldehyde strategy. These investigations supplied a practical approach for site specific modification of proteins with N-terminal serine or threonine to achieve improved homogeneity of conjugates as well as enhanced pharmacological properties.Bioconjugate Chemistry 12/2013; 25(1). DOI:10.1021/bc400435u · 4.82 Impact Factor
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ABSTRACT: Live-attenuated influenza vaccines (LAIVs) have the potential to generate CD8 T cell immunity that may limit the virulence of an antigenically shifted influenza strain in a population lacking protective Abs. However, current LAIVs exert limited T cell immunity restricted to the vaccine strains. One approach to improve LAIV-induced T cell responses is the use of specific adjuvants to enhance T cell priming by respiratory dendritic cells, but this hypothesis has not been addressed. In this study, we assessed the effect of the TLR3 ligand polyinosinic-polycytidylic acid (poly IC) on CD8 T cell immunity and protection elicited by LAIVs. Mucosal treatment with poly IC shortly after vaccination enhanced respiratory dendritic cell function, CD8 T cell formation, and production of neutralizing Abs. This adjuvant effect of poly IC was dependent on amplification of TLR3 signaling by nonhematopoietic radioresistant cells and enhanced mouse protection to homosubtypic, as well as heterosubtypic, virus challenge. Our findings indicate that mucosal TLR3 ligation may be used to improve CD8 T cell responses to replicating vaccines, which has implications for protection in the absence of pre-existing Ab immunity.The Journal of Immunology 06/2014; 193(3). DOI:10.4049/jimmunol.1400222 · 5.36 Impact Factor