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<title xml:lang="en">Multivalent Fusion Protein Vaccine for Lymphatiac filariasis</title>
<author>
<name sortKey="Dakshinamoorthy, Gajalakshmi" sort="Dakshinamoorthy, Gajalakshmi" uniqKey="Dakshinamoorthy G" first="Gajalakshmi" last="Dakshinamoorthy">Gajalakshmi Dakshinamoorthy</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Samykutty, Abhilash Kumble" sort="Samykutty, Abhilash Kumble" uniqKey="Samykutty A" first="Abhilash Kumble" last="Samykutty">Abhilash Kumble Samykutty</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Munirathinam, Gnanasekar" sort="Munirathinam, Gnanasekar" uniqKey="Munirathinam G" first="Gnanasekar" last="Munirathinam">Gnanasekar Munirathinam</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Reddy, Maryada Venkatarami" sort="Reddy, Maryada Venkatarami" uniqKey="Reddy M" first="Maryada Venkatarami" last="Reddy">Maryada Venkatarami Reddy</name>
<affiliation>
<nlm:aff id="A2">Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442102, Maharashtra, India</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
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<idno type="pmid">23036503</idno>
<idno type="pmc">3554871</idno>
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<idno type="RBID">PMC:3554871</idno>
<idno type="doi">10.1016/j.vaccine.2012.09.055</idno>
<date when="2012">2012</date>
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<title xml:lang="en" level="a" type="main">Multivalent Fusion Protein Vaccine for Lymphatiac filariasis</title>
<author>
<name sortKey="Dakshinamoorthy, Gajalakshmi" sort="Dakshinamoorthy, Gajalakshmi" uniqKey="Dakshinamoorthy G" first="Gajalakshmi" last="Dakshinamoorthy">Gajalakshmi Dakshinamoorthy</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Samykutty, Abhilash Kumble" sort="Samykutty, Abhilash Kumble" uniqKey="Samykutty A" first="Abhilash Kumble" last="Samykutty">Abhilash Kumble Samykutty</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Munirathinam, Gnanasekar" sort="Munirathinam, Gnanasekar" uniqKey="Munirathinam G" first="Gnanasekar" last="Munirathinam">Gnanasekar Munirathinam</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Reddy, Maryada Venkatarami" sort="Reddy, Maryada Venkatarami" uniqKey="Reddy M" first="Maryada Venkatarami" last="Reddy">Maryada Venkatarami Reddy</name>
<affiliation>
<nlm:aff id="A2">Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442102, Maharashtra, India</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name>
<affiliation>
<nlm:aff id="A1">Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Vaccine</title>
<idno type="ISSN">0264-410X</idno>
<idno type="eISSN">1873-2518</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
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<div type="abstract" xml:lang="en">
<p id="P2">Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of
<italic>Brugia malayi</italic>
, heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of
<italic>B. malayi</italic>
L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against
<italic>B. malayi</italic>
L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">8406899</journal-id>
<journal-id journal-id-type="pubmed-jr-id">7945</journal-id>
<journal-id journal-id-type="nlm-ta">Vaccine</journal-id>
<journal-id journal-id-type="iso-abbrev">Vaccine</journal-id>
<journal-title-group>
<journal-title>Vaccine</journal-title>
</journal-title-group>
<issn pub-type="ppub">0264-410X</issn>
<issn pub-type="epub">1873-2518</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23036503</article-id>
<article-id pub-id-type="pmc">3554871</article-id>
<article-id pub-id-type="doi">10.1016/j.vaccine.2012.09.055</article-id>
<article-id pub-id-type="manuscript">NIHMS410997</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Multivalent Fusion Protein Vaccine for Lymphatiac filariasis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Dakshinamoorthy</surname>
<given-names>Gajalakshmi</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Samykutty</surname>
<given-names>Abhilash Kumble</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Munirathinam</surname>
<given-names>Gnanasekar</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Reddy</surname>
<given-names>Maryada Venkatarami</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kalyanasundaram</surname>
<given-names>Ramaswamy</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Department of Biomedical Sciences, U of I College of medicine at Rockford, IL-61107, USA</aff>
<aff id="A2">
<label>2</label>
Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram-442102, Maharashtra, India</aff>
<author-notes>
<corresp id="FN1">Address for correspondence and reprint requests to: Dr. K. Ramaswamy, Department of Biomedical Sciences, 1601 Parkview Avenue, College of Medicine, University of Illinois, Rockford, IL- 61107.
<email>ramswamy@uic.edu</email>
, Phone: (815) 395-5696, Fax: (815) 395-5684</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>1</day>
<month>10</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>02</day>
<month>10</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub">
<day>15</day>
<month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>15</day>
<month>3</month>
<year>2014</year>
</pub-date>
<volume>31</volume>
<issue>12</issue>
<fpage>1616</fpage>
<lpage>1622</lpage>
<permissions>
<copyright-statement>© 2012 Elsevier Ltd. All rights reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract>
<p id="P2">Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of
<italic>Brugia malayi</italic>
, heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of
<italic>B. malayi</italic>
L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against
<italic>B. malayi</italic>
L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human.</p>
</abstract>
<kwd-group>
<kwd>Multivalent vaccine</kwd>
<kwd>small Heat Shock Proteins</kwd>
<kwd>Abundant Larval transcript-2</kwd>
<kwd>Tetraspanin</kwd>
<kwd>Antibody Dependent cellular cytotoxicty</kwd>
<kwd>Lymphatic Filariasis</kwd>
</kwd-group>
<funding-group>
<award-group>
<funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
<award-id>R56 AI064745 || AI</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
<award-id>R01 AI064745 || AI</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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