Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

Herrmann, Valerie L.; Hartmayer, Carmen; Planz, Oliver; Gröttrup, Marcus

Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease

Dateien

Herrmann_0-308587.pdfGröße: 899.2 KBDownloads: 548

Datum

2015

Autor:innen

Herrmann, Valerie L.

Hartmayer, Carmen

Planz, Oliver

Gröttrup, Marcus

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of Controlled Release. 2015, 216, pp. 121-131. ISSN 0168-3659. eISSN 1873-4995. Available under: doi: 10.1016/j.jconrel.2015.08.019

Zusammenfassung

Current influenza virus vaccines aim to elicit antibodies directed toward viral surface glycoproteins, which however are prone to antigenic drift. Cytotoxic T lymphocytes (CTLs) can exhibit heterosubtypic immunity against most influenza A viruses. In our study, we encapsulated the highly conserved, immunodominant, HLA-A0201 restricted epitope from the influenza virus matrix protein M1_58-66 together with TLR ligands in biodegradable poly(d,l-lactide-co-glycolide) (PLGA) microspheres. Subcutaneous immunization of transgenic mice expressing chimeric HLA-A0201 molecules with these microspheres induced a strong and sustained CTL response which sufficed to prevent replication of a recombinant vaccinia virus expressing the influenza A virus (IAV) matrix protein but not the replication of IAV in the lung. However, subcutaneous priming followed by intranasal boosting with M158-66 bearing PLGA microspheres was able to induce vigorous CTL responses both in the lung and spleen of mice which interfered with IAV replication, weight loss, and infection-related death. Taken together, vaccination with well-defined and highly conserved IAV-derived CTL epitopes encapsulated into clinically compatible PLGA microspheres contribute to the control of influenza A virus infections. The promptitude and broad reactivity of the CTL response may help to attenuate pandemic outbreaks of influenza viruses.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Cytotoxic T lymphocytes, Influenza A virus, Lung, Mucosal immunity, PLGA microspheres, Vaccination

Zitieren

ISO 690

HERRMANN, Valerie L., Carmen HARTMAYER, Oliver PLANZ, Marcus GRÖTTRUP, 2015. Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease. In: Journal of Controlled Release. 2015, 216, pp. 121-131. ISSN 0168-3659. eISSN 1873-4995. Available under: doi: 10.1016/j.jconrel.2015.08.019

BibTex

@article{Herrmann2015Cytot-32304,
  year={2015},
  doi={10.1016/j.jconrel.2015.08.019},
  title={Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses the infectious disease},
  volume={216},
  issn={0168-3659},
  journal={Journal of Controlled Release},
  pages={121--131},
  author={Herrmann, Valerie L. and Hartmayer, Carmen and Planz, Oliver and Gröttrup, Marcus}
}

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