Replicon RNA Viral Vectors as Vaccines
Identifieur interne : 000796 ( Pmc/Curation ); précédent : 000795; suivant : 000797Replicon RNA Viral Vectors as Vaccines
Auteurs : Kenneth LundstromSource :
- Vaccines [ 2076-393X ] ; 2016.
Abstract
Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.
Url:
DOI: 10.3390/vaccines4040039
PubMed: 27827980
PubMed Central: 5192359
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Replicon RNA Viral Vectors as Vaccines</title><author><name sortKey="Lundstrom, Kenneth" sort="Lundstrom, Kenneth" uniqKey="Lundstrom K" first="Kenneth" last="Lundstrom">Kenneth Lundstrom</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27827980</idno><idno type="pmc">5192359</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192359</idno><idno type="RBID">PMC:5192359</idno><idno type="doi">10.3390/vaccines4040039</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000796</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000796</idno><idno type="wicri:Area/Pmc/Curation">000796</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000796</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Replicon RNA Viral Vectors as Vaccines</title><author><name sortKey="Lundstrom, Kenneth" sort="Lundstrom, Kenneth" uniqKey="Lundstrom K" first="Kenneth" last="Lundstrom">Kenneth Lundstrom</name></author></analytic><series><title level="j">Vaccines</title><idno type="eISSN">2076-393X</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Delrue, I" uniqKey="Delrue I">I. Delrue</name></author><author><name sortKey="Verzele, D" uniqKey="Verzele D">D. Verzele</name></author><author><name sortKey="Madder, A" uniqKey="Madder A">A. Madder</name></author><author><name sortKey="Nauwynck, H J" uniqKey="Nauwynck H">H.J. Nauwynck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, M P" uniqKey="Deng M">M.P. Deng</name></author><author><name sortKey="Hu, Z H" uniqKey="Hu Z">Z.H. Hu</name></author><author><name sortKey="Wan, H L" uniqKey="Wan H">H.L. Wan</name></author><author><name sortKey="Deng, F" uniqKey="Deng F">F. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Vaccines (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Vaccines (Basel)</journal-id><journal-id journal-id-type="publisher-id">vaccines</journal-id><journal-title-group><journal-title>Vaccines</journal-title></journal-title-group><issn pub-type="epub">2076-393X</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27827980</article-id><article-id pub-id-type="pmc">5192359</article-id><article-id pub-id-type="doi">10.3390/vaccines4040039</article-id><article-id pub-id-type="publisher-id">vaccines-04-00039</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Replicon RNA Viral Vectors as Vaccines</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lundstrom</surname><given-names>Kenneth</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Borges</surname><given-names>Olga</given-names></name><role>Academic Editor</role></contrib></contrib-group><aff id="af1-vaccines-04-00039">PanTherapeutics, CH 1095 Lutry, Switzerland;<email>lundstromkenneth@gmail.com</email>; Tel.: +41-79-776-6351</aff><pub-date pub-type="epub"><day>07</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2016</year></pub-date><volume>4</volume><issue>4</issue><elocation-id>39</elocation-id><history><date date-type="received"><day>13</day><month>7</month><year>2016</year></date><date date-type="accepted"><day>28</day><month>10</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 by the author; licensee MDPI, Basel, Switzerland.</copyright-statement><copyright-year>2016</copyright-year><license><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.</p></abstract><kwd-group><kwd>alphaviruses</kwd><kwd>flaviviruses</kwd><kwd>measles viruses</kwd><kwd>rhabdoviruses</kwd><kwd>antibodies</kwd><kwd>infectious diseases</kwd><kwd>tumors</kwd><kwd>disease protection</kwd></kwd-group></article-meta></front><floats-group><fig id="vaccines-04-00039-f001" position="float"><label>Figure 1</label><caption><p>SFV-Based Expression Systems. (<bold>A</bold>) Replication-deficient system. In vitro transcribed RNA from expression and helper vectors are transfected into BHK-21 cells for generation of replication-deficient particles; (<bold>B</bold>) Replication-proficient system. In vitro transcribed RNA from full-length vector is transfected into BHK-21 cells for generation of replication-proficient particles; (<bold>C</bold>) DNA layered system. Plasmid DNA is transfected into host cells. 26S, SFV26S subgenomic promoter; CMV, cytomegalovirus promoter; pA, polyadenylation signal; SP6, SP6 phage RNA polymerase promoter.</p></caption><graphic xlink:href="vaccines-04-00039-g001"></graphic></fig><fig id="vaccines-04-00039-f002" position="float"><label>Figure 2</label><caption><p>Kunjin Virus-Based Expression Systems. Expression vector based on Kunjin virus RNA and DNA expression systems. 3′ UTR, 3′ untranslated region; 5′ UTR, 5′ untranslated region; C20, first 20 amino acids of KUN C protein; CMV, cytomegalovirus promoter; E22, 22 last amino acids of KUN E protein; F, FMDV (foot-and-mouse disease virus) 2A autoprotease; HDVr, hepatitis delta virus ribozyme; ns1-5, nonstructural proteins; pA, polyadenylation signal; SP6, SP6 phage RNA polymerase promoter; U, mouse ubiquitin sequence.</p></caption><graphic xlink:href="vaccines-04-00039-g002"></graphic></fig><fig id="vaccines-04-00039-f003" position="float"><label>Figure 3</label><caption><p>Measles Virus-Based Expression system. The measles virus structural proteins are flanked by T7 RNA polymerase promoter and the T7 RNA polymerase terminator. Foreign genes can be inserted between the P and M or H and L genes. H, MV hemagglutinin; L, MV L protein; M, MV matrix protein; N, MV nucleocapsid protein; T7, T7 RNA polymerase promoter; T7 term, T7 RNA polymerase terminator.</p></caption><graphic xlink:href="vaccines-04-00039-g003"></graphic></fig><fig id="vaccines-04-00039-f004" position="float"><label>Figure 4</label><caption><p>Rabies Virus-Based Expression Systems. The structural genes are from the HEP-Flury strain except the G protein from the CVS strain. Foreign genes can be inserted between the N and P or G and L genes, respectively. CMV, cytomegalovirus promoter; G, rabies G protein; L, rabies L protein; M, rabies matrix protein; N, rabies nucleocapsid protein.</p></caption><graphic xlink:href="vaccines-04-00039-g004"></graphic></fig><fig id="vaccines-04-00039-f005" position="float"><label>Figure 5</label><caption><p>Schematic Presentation of the Life-Cycle of Self-Replicating RNA Viruses and Their Advantages. Several cell receptors are recognized providing a broad range of susceptible host cells. RNA released in the cytoplasm is immediately subjected to RNA replication and translation. Extreme RNA replication is the basis for highly efficient transgene expression.</p></caption><graphic xlink:href="vaccines-04-00039-g005"></graphic></fig><table-wrap id="vaccines-04-00039-t001" position="float"><object-id pub-id-type="pii">vaccines-04-00039-t001_Table 1</object-id><label>Table 1</label><caption><p>Self-replicating RNA viral vector-based immunizations against viral diseases.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Virus</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Vector</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Immunization</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Response</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td rowspan="6" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Influenza</td><td align="center" valign="middle" rowspan="1" colspan="1">NP</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">systemic NP immune response</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B35-vaccines-04-00039" ref-type="bibr">35</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HA</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">chicken</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against influenza virus</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B36-vaccines-04-00039" ref-type="bibr">36</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HA</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">swine</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against influenza virus</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B37-vaccines-04-00039" ref-type="bibr">37</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HA</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">swine</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against influenza virus</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B38-vaccines-04-00039" ref-type="bibr">38</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HA</td><td align="center" valign="middle" rowspan="1" colspan="1">rMV</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">neutralizing Abs</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B39-vaccines-04-00039" ref-type="bibr">39</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">cHA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VSV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against influenza virus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B40-vaccines-04-00039" ref-type="bibr">40</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">HIV</td><td align="center" valign="middle" rowspan="1" colspan="1">Gag</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against HIV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B41-vaccines-04-00039" ref-type="bibr">41</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Env</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">neutralizing Abs, humoral response</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B42-vaccines-04-00039" ref-type="bibr">42</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">gp41</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV-VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">generation of mAbs</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B43-vaccines-04-00039" ref-type="bibr">43</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Env</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV DNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">T cell and IgG immune responses</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B44-vaccines-04-00039" ref-type="bibr">44</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">SIV</td><td align="center" valign="middle" rowspan="1" colspan="1">Gag-Pol</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against SIV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B45-vaccines-04-00039" ref-type="bibr">45</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Env</td><td align="center" valign="middle" rowspan="1" colspan="1">VSV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" rowspan="1" colspan="1">neutralizing Abs </td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B46-vaccines-04-00039" ref-type="bibr">46</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Gag-Env</td><td align="center" valign="middle" rowspan="1" colspan="1">VSV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against SIV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B47-vaccines-04-00039" ref-type="bibr">47</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Gag-Env</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RABV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against SIV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B48-vaccines-04-00039" ref-type="bibr">48</xref>]</td></tr><tr><td rowspan="5" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Ebola</td><td align="center" valign="middle" rowspan="1" colspan="1">GP</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">guinea pig</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against Ebola</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B49-vaccines-04-00039" ref-type="bibr">49</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">GP</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">primate</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against Ebola</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B50-vaccines-04-00039" ref-type="bibr">50</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">GP</td><td align="center" valign="middle" rowspan="1" colspan="1">VSV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against Ebola</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B51-vaccines-04-00039" ref-type="bibr">51</xref>,<xref rid="B52-vaccines-04-00039" ref-type="bibr">52</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">GP, NP</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against Ebola</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B53-vaccines-04-00039" ref-type="bibr">53</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NP</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against Ebola</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B54-vaccines-04-00039" ref-type="bibr">54</xref>]</td></tr><tr><td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Lassa</td><td align="center" valign="middle" rowspan="1" colspan="1">G</td><td align="center" valign="middle" rowspan="1" colspan="1">VSV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">guinea pig</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against Lassa</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B55-vaccines-04-00039" ref-type="bibr">55</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">G</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">guinea pig</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against Lassa</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B56-vaccines-04-00039" ref-type="bibr">56</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SARS-CoV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">G</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against SARS-CoV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B57-vaccines-04-00039" ref-type="bibr">57</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MERS-CoV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">G</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against SARS-CoV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B58-vaccines-04-00039" ref-type="bibr">58</xref>]</td></tr><tr><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">RSV</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">rat</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against RSV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B39-vaccines-04-00039" ref-type="bibr">39</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE LNPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against RSV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B59-vaccines-04-00039" ref-type="bibr">59</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">primate</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against RSV </td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B60-vaccines-04-00039" ref-type="bibr">60</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MPV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">F</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">primate</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against MPV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B60-vaccines-04-00039" ref-type="bibr">60</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Dengue</td><td align="center" valign="middle" rowspan="1" colspan="1">DV2-HBsAg</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">neutralizing Abs</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B61-vaccines-04-00039" ref-type="bibr">61</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">DV2</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against dengue virus</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B62-vaccines-04-00039" ref-type="bibr">62</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">prME-E85</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against dengue virus</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B63-vaccines-04-00039" ref-type="bibr">63</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">prME-E85</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against dengue virus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B64-vaccines-04-00039" ref-type="bibr">64</xref>]</td></tr><tr><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">HBV</td><td align="center" valign="middle" rowspan="1" colspan="1">MHB</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV-VSV G</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against HBV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B65-vaccines-04-00039" ref-type="bibr">65</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">DV2-HBsAg</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against HBV</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B62-vaccines-04-00039" ref-type="bibr">62</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HBsAg</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">macaques</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against HBV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B66-vaccines-04-00039" ref-type="bibr">66</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CMV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">gB-pp65/IE1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">human</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">neutralizing Abs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B67-vaccines-04-00039" ref-type="bibr">67</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p>Abs, antibodies; cHA, chimeric hemagglutinin; CMV, cytomegalovirus; DV2, dengue virus 2; G, glycoprotein; HA, hemagglutinin; HBV, hepatitis B virus; HBsAg, HBV surface antigen; LNPs, lipid nanoparticles; mAbs, monoclonal antibodies; MERS-CoV, Middle East respiratory syndrome coronavirus; MV, measles virus; MPV, metapneumonia virus; NP, nucleoprotein; RABV, rabies virus; RSV, respiratory syncytial virus; SARS-CoV, severe acute respiratory syndrome coronavirus; SFV, Semliki Forest virus; VEE, Venezuelan equine encephalitis virus; VLPs, virus-like particles.</p></fn></table-wrap-foot></table-wrap><table-wrap id="vaccines-04-00039-t002" position="float"><object-id pub-id-type="pii">vaccines-04-00039-t002_Table 2</object-id><label>Table 2</label><caption><p>Self-Replicating RNA Viral Vector-Based Immunizations against Infectious Diseases.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Agent</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Vector</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Immunization</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Response</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>P. falciparum</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">Ag Pf332</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs/RNA</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">immunological memory</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B68-vaccines-04-00039" ref-type="bibr">68</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>M. tuberculosis</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">Ag 85A</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN DNA</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against <italic>M.</italic><italic>tuberculosis</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B69-vaccines-04-00039" ref-type="bibr">69</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>C. botulinum</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">BoNTA-Hc</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV DNA</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">Ab and lymphoproliferative response</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B70-vaccines-04-00039" ref-type="bibr">70</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>B. abortus</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">IF3</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against <italic>Brucella</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B71-vaccines-04-00039" ref-type="bibr">71</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>B. antracis</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">PA</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against <italic>B. antracis</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B72-vaccines-04-00039" ref-type="bibr">72</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Malaria</td><td align="center" valign="middle" rowspan="1" colspan="1">CS</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against malaria</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B73-vaccines-04-00039" ref-type="bibr">73</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><italic>L. monocytogenes</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">OVA</td><td align="center" valign="middle" rowspan="1" colspan="1">VSV-GP</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">protection against <italic>Listeria</italic></td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B74-vaccines-04-00039" ref-type="bibr">74</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Prion</td><td align="center" valign="middle" rowspan="1" colspan="1">PRNP</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" rowspan="1" colspan="1">monoclonal Abs</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B75-vaccines-04-00039" ref-type="bibr">75</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Staphylococcus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SEB</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">mouse</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">protection against enterotoxin</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B76-vaccines-04-00039" ref-type="bibr">76</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p>Abs, antibodies; CS, circumsporozoite protein; IF3, translation initiation factor 3; MV, measles virus; MPV, metapneumonia virus; OVA, ovalbumin; PRNP, prion protein; SEB, staphylococcus enterotoxin B; SFV, Semliki Forest virus; SIN, Sindbis virus; VEE, Venezuelan equine encephalitis virus; VLPs, virus-like particles; VSV-GP, vesicular stomatitis virus pseudotyped with lymphocytic choriomeningitis glycoprotein.</p></fn></table-wrap-foot></table-wrap><table-wrap id="vaccines-04-00039-t003" position="float"><object-id pub-id-type="pii">vaccines-04-00039-t003_Table 3</object-id><label>Table 3</label><caption><p>Self-Replicating RNA Viral Vector-Based Immunizations against Cancers.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Cancer</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Target</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Vector</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Response</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Reference</th></tr></thead><tbody><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Brain</td><td align="center" valign="middle" rowspan="1" colspan="1">GFP, SLAM, EGFR</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">replication in/lysis of cancer cells</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B79-vaccines-04-00039" ref-type="bibr">79</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Endostatin</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B89-vaccines-04-00039" ref-type="bibr">89</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">miR-124</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV-miR-124</td><td align="center" valign="middle" rowspan="1" colspan="1">prolonged survival</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B90-vaccines-04-00039" ref-type="bibr">90</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IL-12</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV-IL-12</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">prolonged survival</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B91-vaccines-04-00039" ref-type="bibr">91</xref>,<xref rid="B92-vaccines-04-00039" ref-type="bibr">92</xref>,<xref rid="B93-vaccines-04-00039" ref-type="bibr">93</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Breast</td><td align="center" valign="middle" rowspan="1" colspan="1">CEA</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor growth delay, better survival</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B83-vaccines-04-00039" ref-type="bibr">83</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Neu</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN DNA</td><td align="center" valign="middle" rowspan="1" colspan="1">immune responses, tumor protection</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B94-vaccines-04-00039" ref-type="bibr">94</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Neu</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs + DCs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor regression by transduced DCs</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B95-vaccines-04-00039" ref-type="bibr">95</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEGFR-2</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">tumor inhibition</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B96-vaccines-04-00039" ref-type="bibr">96</xref>]</td></tr><tr><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Cervical</td><td align="center" valign="middle" rowspan="1" colspan="1">HPV E6, 7</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor eradication</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B97-vaccines-04-00039" ref-type="bibr">97</xref>,<xref rid="B98-vaccines-04-00039" ref-type="bibr">98</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HPV E7</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">eradication of existing tumors</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B99-vaccines-04-00039" ref-type="bibr">99</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">HPV E7 Epitope</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Kunjin VLPs/RNA/DNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">tumor protection in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B88-vaccines-04-00039" ref-type="bibr">88</xref>]</td></tr><tr><td rowspan="7" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Colon</td><td align="center" valign="middle" rowspan="1" colspan="1">GM-CSF</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">regression of tumors and metastasis</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B87-vaccines-04-00039" ref-type="bibr">87</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">VEGFR-2</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">reduced tumor and metastasis growth</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B96-vaccines-04-00039" ref-type="bibr">96</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">LacZ</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV RNA</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor protection in mice</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B100-vaccines-04-00039" ref-type="bibr">100</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">Lac Z</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">anti-tumor CD8+ T-cell immunity</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B101-vaccines-04-00039" ref-type="bibr">101</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IL-12</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor elimination</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B102-vaccines-04-00039" ref-type="bibr">102</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">SFV</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor growth inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B103-vaccines-04-00039" ref-type="bibr">103</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IL-18</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">tumor regression in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B104-vaccines-04-00039" ref-type="bibr">104</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Liver</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IL-12</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">anti-tumor responses in woodchucks</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B105-vaccines-04-00039" ref-type="bibr">105</xref>,<xref rid="B106-vaccines-04-00039" ref-type="bibr">106</xref>]</td></tr><tr><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Lung</td><td align="center" valign="middle" rowspan="1" colspan="1">HPV E6/E7</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV + Sun + Rad</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor-free survival</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B107-vaccines-04-00039" ref-type="bibr">107</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">HPV E7-CRT</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">long-term anti-tumor effect</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B108-vaccines-04-00039" ref-type="bibr">108</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">EGFP</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">apoptosis, tumor regression in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B109-vaccines-04-00039" ref-type="bibr">109</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Melanoma</td><td align="center" valign="middle" rowspan="1" colspan="1">GM-CSF</td><td align="center" valign="middle" rowspan="1" colspan="1">Kunjin VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor regression</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B87-vaccines-04-00039" ref-type="bibr">87</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">VEGF-2-IL-12 + Sur + β-hCG</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B110-vaccines-04-00039" ref-type="bibr">110</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">TRP-2</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">humoral and cellular immunity</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B111-vaccines-04-00039" ref-type="bibr">111</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Tyr</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">T-cell responses, tumor protection in mice</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B112-vaccines-04-00039" ref-type="bibr">112</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Ovarian</td><td align="center" valign="middle" rowspan="1" colspan="1">CEA, NIS</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">superior dual therapy</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B81-vaccines-04-00039" ref-type="bibr">81</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IL-12</td><td align="center" valign="middle" rowspan="1" colspan="1">SIN VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor targeting, eradication</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B113-vaccines-04-00039" ref-type="bibr">113</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">IL-18</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">therapeutic anti-tumor response</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B91-vaccines-04-00039" ref-type="bibr">91</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">GM-CSF</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">tumor growth inhibition</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B114-vaccines-04-00039" ref-type="bibr">114</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Pancreatic</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Matrix protein</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VSV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">killing of tumor cells in vitro and in vivo</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B85-vaccines-04-00039" ref-type="bibr">85</xref>]</td></tr><tr><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Prostate</td><td align="center" valign="middle" rowspan="1" colspan="1">CEA</td><td align="center" valign="middle" rowspan="1" colspan="1">MV</td><td align="center" valign="middle" rowspan="1" colspan="1">replication in/lysis of cancer cells</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B79-vaccines-04-00039" ref-type="bibr">79</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">PSMA</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">cellular and humoral immunity in mice</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B115-vaccines-04-00039" ref-type="bibr">115</xref>]</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">STEAP</td><td align="center" valign="middle" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">CD8+ T-cell response, tumor growth delay</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B116-vaccines-04-00039" ref-type="bibr">116</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PSCA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">DNA + VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">long-term protective immune response</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B117-vaccines-04-00039" ref-type="bibr">117</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Sarcoma</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PSA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">VEE VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">PSA-cell clearance, tumor growth delay</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B118-vaccines-04-00039" ref-type="bibr">118</xref>]</td></tr><tr><td rowspan="2" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Skin</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV</td><td align="center" valign="middle" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" rowspan="1" colspan="1">tumor growth inhibition</td><td align="center" valign="middle" rowspan="1" colspan="1">[<xref rid="B103-vaccines-04-00039" ref-type="bibr">103</xref>]</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">P1A</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">SFV VLPs</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">strong CTL-response, tumor protection</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B119-vaccines-04-00039" ref-type="bibr">119</xref>]</td></tr></tbody></table><table-wrap-foot><fn><p>CEA, carcinoembryonic antigen; CRT, calreticulin; CTL, cytotoxic T lymphocyte; EGFP, enhanced green fluorescent protein; EGFR, epidermal growth factor receptor; GFP, green fluorescent protein; GM-CSF, granulocyte macrophage colony-stimulating factor; HPV, human papilloma virus; MV, measles virus; NIS, sodium iodide symporter; PSMA, prostate-specific membrane antigen; PSCA, prostate stem cell antigen; RABV, rabies virus; SFV, Semliki Forest virus; SIN, Sindbis virus; SLAM, signaling lymphocytic activation molecule; STEAP, six-transmembrane epithelial antigen of the prostate; Sun, sunitab; Sur, survivin; TRP, tyrosine-related protein; Tyr, melanoma antigen tyrosinase; VEE, Venezuelan equine encephalitis virus; VEGFR, vascular endothelial growth factor receptor; VLPs, virus-like particles; VSV, vesicular stomatitis virus.</p></fn></table-wrap-foot></table-wrap><table-wrap id="vaccines-04-00039-t004" position="float"><object-id pub-id-type="pii">vaccines-04-00039-t004_Table 4</object-id><label>Table 4</label><caption><p>Comparison of Self-replicating RNA Viral Vectors with other Viral Vectors.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Viral Vector</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Genome</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Capacity</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Special Features</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Alphavirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ssRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">6–8 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">broad host range, high titer, cytoplasmic RNA, extreme transient expression, no chromosomal integration, choice of DNA, RNA replicon and particle delivery</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Flavivirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ssRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">broad host range, packaging system, choice of DNA, RNA replicon and particle delivery</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Measles virus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ssRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">packaging cell line, measles virus strains for immunization, cytoplasmic RNA</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Rhabdovirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ssRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">reverse genetics systems, broad host range cytoplasmic RNA</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Adenovirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">dsDNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>8 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">broad host range, packaging cell line, nuclear translocation necessary, transient expression, potential integration</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">AAV</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">ssDNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><4 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">multiple AAV serotypes for avoiding immune responses, nuclear translocation necessary, chromosomal integration</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Herpes simplex virus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">dsDNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">30–40 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">large packaging capacity, nuclear translocation necessary, latent long-term transgene expression after integration</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Lentivirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">dsRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">8 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">transduction of dividing and non-dividing cells, nuclear translocation necessary, chromosomal integration</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Retrovirus</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">dsRNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">4 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">transduction of only dividing cells, nuclear translocation necessary, chromosomal integration</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Vaccinia</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">dsDNA</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">25 kb</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">large packaging capacity, nuclear translocation necessary</td></tr></tbody></table><table-wrap-foot><fn><p>AAV, adeno-associated virus; dsDNA, double-stranded DNA; ssDNA, single-stranded DNA; ssRNA, single-stranded RNA.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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