Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins
Identifieur interne : 000E24 ( Pmc/Curation ); précédent : 000E23; suivant : 000E25Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins
Auteurs : Seyed Davoud Jazayeri ; Chit Laa PohSource :
- Vaccines [ 2076-393X ] ; 2019.
Abstract
Vaccination is still the most efficient way to prevent an infection with influenza viruses. Nevertheless, existing commercial vaccines face serious limitations such as availability during epidemic outbreaks and their efficacy. Existing seasonal influenza vaccines mostly induce antibody responses to the surface proteins of influenza viruses, which frequently change due to antigenic shift and or drift, thus allowing influenza viruses to avoid neutralizing antibodies. Hence, influenza vaccines need a yearly formulation to protect against new seasonal viruses. A broadly protective or universal influenza vaccine must induce effective humoral as well as cellular immunity against conserved influenza antigens, offer good protection against influenza pandemics, be safe, and have a fast production platform. Nanotechnology has great potential to improve vaccine delivery, immunogenicity, and host immune responses. As new strains of human epidemic influenza virus strains could originate from poultry and swine viruses, development of a new universal influenza vaccine will require the immune responses to be directed against viruses from different hosts. This review discusses how the new vaccine platforms and nanoparticles can be beneficial in the development of a broadly protective, universal influenza vaccine.
Url:
DOI: 10.3390/vaccines7040169
PubMed: 31683888
PubMed Central: 6963725
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<front><div type="abstract" xml:lang="en"><p>Vaccination is still the most efficient way to prevent an infection with influenza viruses. Nevertheless, existing commercial vaccines face serious limitations such as availability during epidemic outbreaks and their efficacy. Existing seasonal influenza vaccines mostly induce antibody responses to the surface proteins of influenza viruses, which frequently change due to antigenic shift and or drift, thus allowing influenza viruses to avoid neutralizing antibodies. Hence, influenza vaccines need a yearly formulation to protect against new seasonal viruses. A broadly protective or universal influenza vaccine must induce effective humoral as well as cellular immunity against conserved influenza antigens, offer good protection against influenza pandemics, be safe, and have a fast production platform. Nanotechnology has great potential to improve vaccine delivery, immunogenicity, and host immune responses. As new strains of human epidemic influenza virus strains could originate from poultry and swine viruses, development of a new universal influenza vaccine will require the immune responses to be directed against viruses from different hosts. This review discusses how the new vaccine platforms and nanoparticles can be beneficial in the development of a broadly protective, universal influenza vaccine.</p>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<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">31683888</article-id>
<article-id pub-id-type="pmc">6963725</article-id>
<article-id pub-id-type="doi">10.3390/vaccines7040169</article-id>
<article-id pub-id-type="publisher-id">vaccines-07-00169</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Jazayeri</surname>
<given-names>Seyed Davoud</given-names>
</name>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-8475-6291</contrib-id>
<name><surname>Poh</surname>
<given-names>Chit Laa</given-names>
</name>
<xref rid="c1-vaccines-07-00169" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="af1-vaccines-07-00169">Centre for Virus and Vaccine Research, School of Science and Technology, Sunway University, Subang Jaya 47500, Malaysia;<email>sjazayeri@sunway.edu.my</email>
</aff>
<author-notes><corresp id="c1-vaccines-07-00169"><label>*</label>
Correspondence: <email>pohcl@sunway.edu.my</email>
; Tel.: +603-7491-8622 (ext. 7338); Fax: +603-5635-8633</corresp>
</author-notes>
<pub-date pub-type="epub"><day>01</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><month>12</month>
<year>2019</year>
</pub-date>
<volume>7</volume>
<issue>4</issue>
<elocation-id>169</elocation-id>
<history><date date-type="received"><day>16</day>
<month>8</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>05</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 by the authors.</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. 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>Vaccination is still the most efficient way to prevent an infection with influenza viruses. Nevertheless, existing commercial vaccines face serious limitations such as availability during epidemic outbreaks and their efficacy. Existing seasonal influenza vaccines mostly induce antibody responses to the surface proteins of influenza viruses, which frequently change due to antigenic shift and or drift, thus allowing influenza viruses to avoid neutralizing antibodies. Hence, influenza vaccines need a yearly formulation to protect against new seasonal viruses. A broadly protective or universal influenza vaccine must induce effective humoral as well as cellular immunity against conserved influenza antigens, offer good protection against influenza pandemics, be safe, and have a fast production platform. Nanotechnology has great potential to improve vaccine delivery, immunogenicity, and host immune responses. As new strains of human epidemic influenza virus strains could originate from poultry and swine viruses, development of a new universal influenza vaccine will require the immune responses to be directed against viruses from different hosts. This review discusses how the new vaccine platforms and nanoparticles can be beneficial in the development of a broadly protective, universal influenza vaccine.</p>
</abstract>
<kwd-group><kwd>seasonal influenza vaccine</kwd>
<kwd>universal influenza vaccine</kwd>
<kwd>humoral and cell-mediated immunity</kwd>
<kwd>conserved viral proteins</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><fig id="vaccines-07-00169-f001" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Antigens for universal influenza vaccine development. (<bold>A</bold>
) Neutralizing antibodies against highly conserved hemagglutinin (HA) (major protein of influenza virus) stem can provide broadly protective immune responses and cross-protection. (<bold>B</bold>
) Neutralizing antibodies against the globular head of HA can prevent virus binding to sialic acid and prevent the conformational change that leads to fusion. (<bold>C</bold>
) Anti-neuraminidase (NA) (second major protein of influenza virus) response targets the enzymatic site to prevent virus entry, inhibit replication efficiency, decrease disease severity after infection and cross-protection. (<bold>D</bold>
) Anti-matrix protein 2 (M2) antibodies (third major protein of influenza virus) provide a better cross-protective response due to the high conservation. Non-neutralizing Ab against this domain mediates its mediates protection by antibody-dependent cell-mediated cytotoxicity. (<bold>E</bold>
) matrix protein 1 (M1) is an internal protein which is generally not exposed outside of the virus and needs to be processed by major histocompatibility complex I (MHC I) for CD8 T cell antigen recognition. (<bold>F</bold>
) Highly conserved nucleoproteins (NP) viral proteins being used as a target to CD8 T cells to provide better protection from several infections. (<bold>G</bold>
) CD8 T cells recognize peptides derived from variable (HA and NA) and highly conserved internal proteins (NP and M1) presented by MHC I at the surface of antigen presenting cell (APC)/infected cells via their T cell receptor (TCR). Cytotoxic T lymphocytes (CTL) release cytotoxic granules containing perforin and granzymes which lysis the infected cells. (<bold>H</bold>
) Memory CD4 T cells are required for early Ab and CD8 T cell recruitment responses.</p>
</caption>
<graphic xlink:href="vaccines-07-00169-g001"></graphic>
</fig>
<fig id="vaccines-07-00169-f002" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Advantages and disadvantages of whole peptide/multi-epitope (<bold>A</bold>
), DNA (<bold>B</bold>
), mRNA (<bold>C</bold>
), and virus-like particles (VLP) (<bold>D</bold>
) vaccine platforms for developing a novel universal influenza vaccine: All four vaccine platforms are able to induce humoral and cellular immune responses.</p>
</caption>
<graphic xlink:href="vaccines-07-00169-g002"></graphic>
</fig>
<table-wrap id="vaccines-07-00169-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">vaccines-07-00169-t001_Table 1</object-id>
<label>Table 1</label>
<caption><p>Categories of annual influenza vaccines approved by the Food and Drug Administration (FDA).</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">Type of Vaccine</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Virus Strain</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Trade Name</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Production</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Age</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Immunological Outcomes</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Route</th>
<th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Ref.</th>
</tr>
</thead>
<tbody><tr><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">IIV</td>
<td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Influenza A: H1N1 and H3N2 virus/Influenza B: Victoria and/or Yamagata</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Fluzone</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Eggs</td>
<td align="center" valign="middle" rowspan="1" colspan="1">6–35 m</td>
<td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">Ab immune response</td>
<td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">IM</td>
<td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">[<xref rid="B34-vaccines-07-00169" ref-type="bibr">34</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" rowspan="1" colspan="1">Fluarix</td>
<td align="center" valign="middle" rowspan="1" colspan="1">Eggs</td>
<td align="center" valign="middle" rowspan="1" colspan="1">>6 m</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Flucelvax</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MDCK cells</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>4 y</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">RIV</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Contains the HA ectodomain amino acid sequence of cell-cultured vaccine prototype viruses suggested by WHO</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Flublok</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Recombinant-expression in insect cell line</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">>18 y</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Ab immune response</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IM</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B35-vaccines-07-00169" ref-type="bibr">35</xref>
,<xref rid="B36-vaccines-07-00169" ref-type="bibr">36</xref>
]</td>
</tr>
<tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">LAIV</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Subtypes of H1N1 and H3N2 (influenza A) and one Influenza B</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FluMist</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Eggs</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2–49 y</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Mucosal (nasal) IgA Ab and strong cell-mediated immunity</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">IN</td>
<td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">[<xref rid="B37-vaccines-07-00169" ref-type="bibr">37</xref>
,<xref rid="B38-vaccines-07-00169" ref-type="bibr">38</xref>
,<xref rid="B39-vaccines-07-00169" ref-type="bibr">39</xref>
]</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>Madin–Darby canine kidney (MDCK); intranasal (IN); intramuscular (IM); antibody (Ab); month (m); year (y); inactivated influenza vaccine (IIV); hemagglutinin (HA); recombinant influenza vaccine (RIV); World Health Organization (WHO); live attenuated influenza vaccine (LAIV)</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
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