Abstract:
:Influenza B virus (IBV) is considered a major human pathogen, responsible for seasonal epidemics of acute respiratory illness. Two antigenically distinct IBV hemagglutinin (HA) lineages cocirculate worldwide with little cross-reactivity. Live attenuated influenza virus (LAIV) vaccines have been shown to provide better cross-protective immune responses than inactivated vaccines by eliciting local mucosal immunity and systemic B cell- and T cell-mediated memory responses. We have shown previously that incorporation of temperature-sensitive (ts) mutations into the PB1 and PB2 subunits along with a modified HA epitope tag in the C terminus of PB1 resulted in influenza A viruses (IAV) that are safe and effective as modified live attenuated (att) virus vaccines (IAV att). We explored whether analogous mutations in the IBV polymerase subunits would result in a stable virus with an att phenotype. The PB1 subunit of the influenza B/Brisbane/60/2008 strain was used to incorporate ts mutations and a C-terminal HA tag. Such modifications resulted in a B/Bris att strain with ts characteristics in vitro and an att phenotype in vivo Vaccination studies in mice showed that a single dose of the B/Bris att candidate stimulated sterilizing immunity against lethal homologous challenge and complete protection against heterologous challenge. These studies show the potential of an alternative LAIV platform for the development of IBV vaccines.IMPORTANCE A number of issues with regard to the effectiveness of the LAIV vaccine licensed in the United States (FluMist) have arisen over the past three seasons (2013-2014, 2014-2015, and 2015-2016). While the reasons for the limited robustness of the vaccine-elicited immune response remain controversial, this problem highlights the critical importance of continued investment in LAIV development and creates an opportunity to improve current strategies so as to develop more efficacious vaccines. Our laboratory has developed an alternative strategy, the incorporation of 2 amino acid mutations and a modified HA tag at the C terminus of PB1, which is sufficient to attenuate the IBV. As a LAIV, this novel vaccine provides complete protection against IBV strains. The availability of attenuated IAV and IBV backbones based on contemporary strains offers alternative platforms for the development of LAIVs that may overcome current limitations.
journal_name
J Viroljournal_title
Journal of virologyauthors
Santos JJS,Finch C,Sutton T,Obadan A,Aguirre I,Wan Z,Lopez D,Geiger G,Gonzalez-Reiche AS,Ferreri L,Perez DRdoi
10.1128/JVI.00056-17subject
Has Abstractpub_date
2017-05-26 00:00:00issue
12eissn
0022-538Xissn
1098-5514pii
JVI.00056-17journal_volume
91pub_type
杂志文章abstract::The specificity of binding of wheat germ ribosomes to mRNA was greatly altered by cleavage of the message. Fragmentation of reovirus mRNA allowed wheat germ ribosomes to bind and protect a variety of internal sequences which were not accessible to ribosomes in the intact message. In experiments using the polycistronic...
journal_title:Journal of virology
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doi:10.1128/JVI.35.3.748-756.1980
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abstract::Whole inactivated virus vaccines from the FL4 cell line protected against challenge with homologous feline immunodeficiency virus (Petaluma strain) but not against a heterologous FIV isolate (GL-8) which is distinct from the Petaluma strain in virus neutralization. Protection was associated with a type-specific neutra...
journal_title:Journal of virology
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doi:10.1128/JVI.69.2.1253-1255.1995
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.69.12.8051-8056.1995
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pub_type: 杂志文章
doi:10.1128/JVI.73.2.897-906.1999
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.684-691.1980
更新日期:1980-12-01 00:00:00
abstract::The replication of the simian herpesvirus SA8 in Vero cells was examined. The time course of replication of the simian herpesvirus SA8 was found to be similar to that of the herpes simplex viruses. Infectious progeny virions were first detectable by 6 h postinfection and were readily released into the extracellular fl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.2.316-324.1984
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pub_type: 杂志文章
doi:10.1128/JVI.72.4.3235-3240.1998
更新日期:1998-04-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00604-10
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.270-280.1999
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pub_type: 杂志文章
doi:10.1128/jvi.76.4.1959-1970.2002
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abstract::Human immunodeficiency virus (HIV) infects human cells by binding to surface CD4 molecules and directly fusing with the cell membrane. Although mouse cells expressing human CD4 bind HIV, they do not become infected, apparently because of a block in membrane fusion. To study this problem, we constructed a recombinant v...
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pub_type: 杂志文章
doi:10.1128/JVI.64.5.2149-2156.1990
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5596-5601.1994
更新日期:1994-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.1998-2005.1999
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