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

tetano

Editor, Senior Moderator
J Control Release. 2015 Aug 11. pii: S0168-3659(15)30065-1. doi: 10.1016/j.jconrel.2015.08.019. [Epub ahead of print]
[h=1]Cytotoxic T cell vaccination with PLGA microspheres interferes with influenza A virus replication in the lung and suppresses infectious disease.[/h] Herrmann VL[SUP]1[/SUP], Hartmayer C[SUP]2[/SUP], Planz O[SUP]3[/SUP], Groettrup M[SUP]4[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Current influenza virus vaccines aim to elicit antibodies directed to viral surface glycoproteins, which however are prone to antigenic drift. Cytotoxic T lymphocytes (CTL) can exhibit heterosubtypic immunity against most influenza A viruses. In our study, we encapsulated the highly conserved, immunodominant, HLA-A*0201 restricted epitope from the influenza virus matrix protein M1[SUB]58-66[/SUB] together with TLR ligands in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Subcutaneous immunization of transgenic mice expressing chimeric HLA-A*0201 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 M1[SUB]58-66[/SUB] 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.
Copyright ? 2015. Published by Elsevier B.V.


[h=4]KEYWORDS:[/h] Cytotoxic T lymphocytes; PLGA microspheres; influenza A virus; lung; mucosal immunity; vaccination

PMID: 26276509 [PubMed - as supplied by publisher]
 
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