Multivalent vaccine formulation with BmVAL-1 and BmALT-2 confer significant protection against challenge infections with Brugia malayi in mice and jirds
Identifieur interne : 002995 ( Pmc/Corpus ); précédent : 002994; suivant : 002996Multivalent vaccine formulation with BmVAL-1 and BmALT-2 confer significant protection against challenge infections with Brugia malayi in mice and jirds
Auteurs : Ramaswamy Kalyanasundaram ; Padmavathi BalumuriSource :
- Research and reports in tropical medicine [ 1179-7282 ] ; 2011.
Abstract
Lymphatic filariasis, a mosquito-borne infection, affects 120 million people in 83 different countries. Mass drug administration is fully underway in several parts of the world to eradicate this infection by year 2020. Drugs alone are highly efficient treatments, but long-term sustainable prophylaxis requires an effective vaccine. No vaccines are available for humans and animals despite several potential candidate vaccine antigens having been identified.
Mice and jirds were vaccinated with monovalent DNA preparations of
Vaccination with monovalent BmVAL-1 vaccine conferred 39% (DNA vaccine) to 54% (DNA prime and protein boost) protection in mice. A similar degree of protection was observed in jirds (50% to 52%). Monovalent BmALT-2 afforded 51% to 75% protection in mice and 58% to 79% protection in jirds. Our testing of a multivalent formulation of BmVAL-1 and BmALT-2, showed 57% to 82% protection in mice and 77% to 85% protection in jirds. A heterologous prime boost approach using the multivalent vaccine gave the highest degree of protection in both mice and jirds. Serological analysis in mice showed that BmVAL-1 vaccination induced an IgG1, IgG2a, and IgG3 antibody response, whereas BmALT-2 vaccination predominantly induced an IgG1 and IgG3 antibody response. Cytokine responses of antigen-responding cells in the spleen secreted predominantly IFN-γ and IL-5 in response to BmVAL-1, and IL-4, and IL-5 in response to BmALT-2.
A multivalent vaccine formulation of BmVAL-1 and BmALT-2 given as a prime boost regimen gave significant protection against lymphatic filariasis caused by
Url:
DOI: 10.2147/RRTM.S13679
PubMed: 21760754
PubMed Central: 3134236
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PMC:3134236Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Multivalent vaccine formulation with BmVAL-1 and BmALT-2 confer significant protection against challenge infections with <italic>Brugia malayi</italic>
in mice and jirds</title>
<author><name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name>
</author>
<author><name sortKey="Balumuri, Padmavathi" sort="Balumuri, Padmavathi" uniqKey="Balumuri P" first="Padmavathi" last="Balumuri">Padmavathi Balumuri</name>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Multivalent vaccine formulation with BmVAL-1 and BmALT-2 confer significant protection against challenge infections with <italic>Brugia malayi</italic>
in mice and jirds</title>
<author><name sortKey="Kalyanasundaram, Ramaswamy" sort="Kalyanasundaram, Ramaswamy" uniqKey="Kalyanasundaram R" first="Ramaswamy" last="Kalyanasundaram">Ramaswamy Kalyanasundaram</name>
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<author><name sortKey="Balumuri, Padmavathi" sort="Balumuri, Padmavathi" uniqKey="Balumuri P" first="Padmavathi" last="Balumuri">Padmavathi Balumuri</name>
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<series><title level="j">Research and reports in tropical medicine</title>
<idno type="eISSN">1179-7282</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Purpose</title>
<p id="P1">Lymphatic filariasis, a mosquito-borne infection, affects 120 million people in 83 different countries. Mass drug administration is fully underway in several parts of the world to eradicate this infection by year 2020. Drugs alone are highly efficient treatments, but long-term sustainable prophylaxis requires an effective vaccine. No vaccines are available for humans and animals despite several potential candidate vaccine antigens having been identified. <italic>Brugia malayi</italic>
vespid venom allergen homolog-like protein (BmVAL-1) and <italic>B. malayi</italic>
abundant larval transcript (BmALT-2) are two of the most promising vaccine candidates. We evaluated various vaccination regimens consisting of DNA and protein antigens and evaluated the potential of monovalent and multivalent vaccine formulations in mice and jird animal models.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P2">Mice and jirds were vaccinated with monovalent DNA preparations of <italic>BmVAL-1</italic>
or <italic>BmALT-2</italic>
in pVAX-1 vector or monovalent protein preparations of rBmVAL-1 and rBmALT-2 in alum using a homologous or heterologous prime boost approach. These vaccine regimens were then compared with a multivalent vaccine formulation consisting of DNA or hybrid protein formulation of the two antigens. Challenge experiments were performed with <italic>B. malayi</italic>
L3 in mice and jirds to evaluate the degree of protection, and immunological parameters were determined in mice and humans to elucidate the characteristics of the protective immune responses.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Vaccination with monovalent BmVAL-1 vaccine conferred 39% (DNA vaccine) to 54% (DNA prime and protein boost) protection in mice. A similar degree of protection was observed in jirds (50% to 52%). Monovalent BmALT-2 afforded 51% to 75% protection in mice and 58% to 79% protection in jirds. Our testing of a multivalent formulation of BmVAL-1 and BmALT-2, showed 57% to 82% protection in mice and 77% to 85% protection in jirds. A heterologous prime boost approach using the multivalent vaccine gave the highest degree of protection in both mice and jirds. Serological analysis in mice showed that BmVAL-1 vaccination induced an IgG1, IgG2a, and IgG3 antibody response, whereas BmALT-2 vaccination predominantly induced an IgG1 and IgG3 antibody response. Cytokine responses of antigen-responding cells in the spleen secreted predominantly IFN-γ and IL-5 in response to BmVAL-1, and IL-4, and IL-5 in response to BmALT-2.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">A multivalent vaccine formulation of BmVAL-1 and BmALT-2 given as a prime boost regimen gave significant protection against lymphatic filariasis caused by <italic>B. malayi</italic>
in mice and jirds. Because putatively immune endemic normal subjects also carry protective antibodies against BmVAL-1 and BmALT-2, developing this multivalent formulation as a prophylactic vaccine against <italic>B. malayi</italic>
for human and veterinary use has great potential.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="en"><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">101562656</journal-id>
<journal-id journal-id-type="pubmed-jr-id">39272</journal-id>
<journal-id journal-id-type="nlm-ta">Res Rep Trop Med</journal-id>
<journal-title-group><journal-title>Research and reports in tropical medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">1179-7282</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21760754</article-id>
<article-id pub-id-type="pmc">3134236</article-id>
<article-id pub-id-type="doi">10.2147/RRTM.S13679</article-id>
<article-id pub-id-type="manuscript">NIHMS299387</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Multivalent vaccine formulation with BmVAL-1 and BmALT-2 confer significant protection against challenge infections with <italic>Brugia malayi</italic>
in mice and jirds</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kalyanasundaram</surname>
<given-names>Ramaswamy</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Balumuri</surname>
<given-names>Padmavathi</given-names>
</name>
</contrib>
<aff id="A1">Department of Biomedical Sciences, College of Medicine, University of Illinois Rockford, IL, USA</aff>
</contrib-group>
<author-notes><corresp id="FN1">Correspondence: Kalyanasundaram R, Professor and Head, Department of Biomedical Sciences, University of Illinois Rockford, College of Medicine, 1601 Parkview Avenue, Rockford, IL 61107, USA, Tel +1 815 395-5696, Fax +1 815 395-5684, <email>ramswamy@uic.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>19</day>
<month>6</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>12</day>
<month>7</month>
<year>2011</year>
</pub-date>
<volume>2011</volume>
<issue>2</issue>
<fpage>45</fpage>
<lpage>56</lpage>
<permissions><copyright-statement>© 2011 Kalyanasundaram and Balumuri, publisher and licensee Dove Medical Press Ltd.</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract><sec id="S1"><title>Purpose</title>
<p id="P1">Lymphatic filariasis, a mosquito-borne infection, affects 120 million people in 83 different countries. Mass drug administration is fully underway in several parts of the world to eradicate this infection by year 2020. Drugs alone are highly efficient treatments, but long-term sustainable prophylaxis requires an effective vaccine. No vaccines are available for humans and animals despite several potential candidate vaccine antigens having been identified. <italic>Brugia malayi</italic>
vespid venom allergen homolog-like protein (BmVAL-1) and <italic>B. malayi</italic>
abundant larval transcript (BmALT-2) are two of the most promising vaccine candidates. We evaluated various vaccination regimens consisting of DNA and protein antigens and evaluated the potential of monovalent and multivalent vaccine formulations in mice and jird animal models.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P2">Mice and jirds were vaccinated with monovalent DNA preparations of <italic>BmVAL-1</italic>
or <italic>BmALT-2</italic>
in pVAX-1 vector or monovalent protein preparations of rBmVAL-1 and rBmALT-2 in alum using a homologous or heterologous prime boost approach. These vaccine regimens were then compared with a multivalent vaccine formulation consisting of DNA or hybrid protein formulation of the two antigens. Challenge experiments were performed with <italic>B. malayi</italic>
L3 in mice and jirds to evaluate the degree of protection, and immunological parameters were determined in mice and humans to elucidate the characteristics of the protective immune responses.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Vaccination with monovalent BmVAL-1 vaccine conferred 39% (DNA vaccine) to 54% (DNA prime and protein boost) protection in mice. A similar degree of protection was observed in jirds (50% to 52%). Monovalent BmALT-2 afforded 51% to 75% protection in mice and 58% to 79% protection in jirds. Our testing of a multivalent formulation of BmVAL-1 and BmALT-2, showed 57% to 82% protection in mice and 77% to 85% protection in jirds. A heterologous prime boost approach using the multivalent vaccine gave the highest degree of protection in both mice and jirds. Serological analysis in mice showed that BmVAL-1 vaccination induced an IgG1, IgG2a, and IgG3 antibody response, whereas BmALT-2 vaccination predominantly induced an IgG1 and IgG3 antibody response. Cytokine responses of antigen-responding cells in the spleen secreted predominantly IFN-γ and IL-5 in response to BmVAL-1, and IL-4, and IL-5 in response to BmALT-2.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">A multivalent vaccine formulation of BmVAL-1 and BmALT-2 given as a prime boost regimen gave significant protection against lymphatic filariasis caused by <italic>B. malayi</italic>
in mice and jirds. Because putatively immune endemic normal subjects also carry protective antibodies against BmVAL-1 and BmALT-2, developing this multivalent formulation as a prophylactic vaccine against <italic>B. malayi</italic>
for human and veterinary use has great potential.</p>
</sec>
</abstract>
<kwd-group><kwd><italic>Brugia malayi</italic>
</kwd>
<kwd>BmALT-2</kwd>
<kwd>BmVAL-1</kwd>
<kwd>vaccine</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>R01 AI064745-04 || 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 AI064745-03 || AI</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
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