A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice
Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Here we describe a conjugate vaccine for cholera prepared via squaric ac...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2015-07, Vol.9 (7), p.e0003881 |
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| creator | Sayeed, Md Abu Bufano, Meagan Kelly Xu, Peng Eckhoff, Grace Charles, Richelle C Alam, Mohammad Murshid Sultana, Tania Rashu, Md Rasheduzzaman Berger, Amanda Gonzalez-Escobedo, Geoffrey Mandlik, Anjali Bhuiyan, Taufiqur Rahman Leung, Daniel T LaRocque, Regina C Harris, Jason B Calderwood, Stephen B Qadri, Firdausi Vann, W F Kováč, Pavol Ryan, Edward T |
| description | Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).
Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. |
| doi_str_mv | 10.1371/journal.pntd.0003881 |
| format | Article |
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Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0003881</identifier><identifier>PMID: 26154421</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Age ; Animals ; Antibodies, Bacterial - immunology ; Bacteriology ; Child ; Child, Preschool ; Cholera ; Cholera - immunology ; Cholera - microbiology ; Cholera - prevention & control ; Cholera Vaccines - administration & dosage ; Cholera Vaccines - chemistry ; Cholera Vaccines - immunology ; Disease Models, Animal ; Female ; Humans ; Immunization ; Immunologic Memory ; Infections ; Male ; Mice ; Middle Aged ; Mucous Membrane - immunology ; O Antigens - administration & dosage ; O Antigens - genetics ; O Antigens - immunology ; Public health ; Sanitation ; Tetanus ; Tetanus Toxin - administration & dosage ; Tetanus Toxin - chemistry ; Tetanus Toxin - immunology ; Vaccines ; Vaccines, Conjugate - administration & dosage ; Vaccines, Conjugate - chemistry ; Vaccines, Conjugate - immunology ; Vibrio cholerae O1 - immunology ; Young Adult</subject><ispartof>PLoS neglected tropical diseases, 2015-07, Vol.9 (7), p.e0003881</ispartof><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice. PLoS Negl Trop Dis 9(7): e0003881. doi:10.1371/journal.pntd.0003881</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-f05dc21cca877688976d0f7162c8db1a7eea8d29564329122472c8b3dc393b433</citedby><cites>FETCH-LOGICAL-c461t-f05dc21cca877688976d0f7162c8db1a7eea8d29564329122472c8b3dc393b433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495926/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495926/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26154421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sayeed, Md Abu</creatorcontrib><creatorcontrib>Bufano, Meagan Kelly</creatorcontrib><creatorcontrib>Xu, Peng</creatorcontrib><creatorcontrib>Eckhoff, Grace</creatorcontrib><creatorcontrib>Charles, Richelle C</creatorcontrib><creatorcontrib>Alam, Mohammad Murshid</creatorcontrib><creatorcontrib>Sultana, Tania</creatorcontrib><creatorcontrib>Rashu, Md Rasheduzzaman</creatorcontrib><creatorcontrib>Berger, Amanda</creatorcontrib><creatorcontrib>Gonzalez-Escobedo, Geoffrey</creatorcontrib><creatorcontrib>Mandlik, Anjali</creatorcontrib><creatorcontrib>Bhuiyan, Taufiqur Rahman</creatorcontrib><creatorcontrib>Leung, Daniel T</creatorcontrib><creatorcontrib>LaRocque, Regina C</creatorcontrib><creatorcontrib>Harris, Jason B</creatorcontrib><creatorcontrib>Calderwood, Stephen B</creatorcontrib><creatorcontrib>Qadri, Firdausi</creatorcontrib><creatorcontrib>Vann, W F</creatorcontrib><creatorcontrib>Kováč, Pavol</creatorcontrib><creatorcontrib>Ryan, Edward T</creatorcontrib><title>A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).
Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Animals</subject><subject>Antibodies, Bacterial - immunology</subject><subject>Bacteriology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cholera</subject><subject>Cholera - immunology</subject><subject>Cholera - microbiology</subject><subject>Cholera - prevention & control</subject><subject>Cholera Vaccines - administration & dosage</subject><subject>Cholera Vaccines - chemistry</subject><subject>Cholera Vaccines - immunology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunologic Memory</subject><subject>Infections</subject><subject>Male</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Mucous Membrane - immunology</subject><subject>O Antigens - administration & dosage</subject><subject>O Antigens - genetics</subject><subject>O Antigens - immunology</subject><subject>Public health</subject><subject>Sanitation</subject><subject>Tetanus</subject><subject>Tetanus Toxin - administration & dosage</subject><subject>Tetanus Toxin - chemistry</subject><subject>Tetanus Toxin - immunology</subject><subject>Vaccines</subject><subject>Vaccines, Conjugate - administration & dosage</subject><subject>Vaccines, Conjugate - chemistry</subject><subject>Vaccines, Conjugate - immunology</subject><subject>Vibrio cholerae O1 - immunology</subject><subject>Young Adult</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNpVkk1vEzEQhlcIREvhHyDwsZVIsPfD3uWAVEWURkqViIZerVl7NnW0awd7tyJ_nRPOR6v25JHnneedsSdJPjI6ZplgX9du8Bba8cb2ekwpzcqSvUpOWZUVo1Rkxetn8UnyLoQ1pUVVlOxtcpJyVuR5yk6Tf5dkcu9a9EAmzq6HFfRI7kApY3F304Oxxq7IfBQ2qExjFFm4dhui4h680UjO57eLC-Iacjcm6oBCMmdkaqEGAlaTX6hcVxsLtidXHlYdxiAWLLEHOwSydH-NJdcID9vYTDTcM7_55fJaXUSOHhQGcot-6L6QG-yc3-65M-gilCy823gDbfQJG2dD1MIqUkJPImavnIadqkfVmwck0eDGKHyfvGmgDfjheJ4lv69-LCfXo9n853RyORupnLN-1NBCq5QpBaUQvCwrwTVtBOOpKnXNQCBCqdOq4HmWVixNcxEzdaZVVmV1nmVnyecDd9O6II_fFiQTKc15WfEiKqYHhXawlnGYDvxWOjByf-H8SoLvjWpRUhQVT6vYkNB5CaLKNHABtOGMoqZ1ZH0_ug11h1rFt_bQvoC-zFhzL1fuQeZ5VVQpj4DzI8C7PwOGXnYmKGxbsOiGXd-0YpxzJqI0P0iVdyF4bJ5sGJW7JX2cVu6WVB6XNJZ9et7iU9HjVmb_AShB50A</recordid><startdate>20150708</startdate><enddate>20150708</enddate><creator>Sayeed, Md Abu</creator><creator>Bufano, Meagan Kelly</creator><creator>Xu, Peng</creator><creator>Eckhoff, Grace</creator><creator>Charles, Richelle C</creator><creator>Alam, Mohammad Murshid</creator><creator>Sultana, Tania</creator><creator>Rashu, Md Rasheduzzaman</creator><creator>Berger, Amanda</creator><creator>Gonzalez-Escobedo, Geoffrey</creator><creator>Mandlik, Anjali</creator><creator>Bhuiyan, Taufiqur Rahman</creator><creator>Leung, Daniel T</creator><creator>LaRocque, Regina C</creator><creator>Harris, Jason B</creator><creator>Calderwood, Stephen B</creator><creator>Qadri, Firdausi</creator><creator>Vann, W F</creator><creator>Kováč, Pavol</creator><creator>Ryan, Edward T</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150708</creationdate><title>A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice</title><author>Sayeed, Md Abu ; Bufano, Meagan Kelly ; Xu, Peng ; Eckhoff, Grace ; Charles, Richelle C ; Alam, Mohammad Murshid ; Sultana, Tania ; Rashu, Md Rasheduzzaman ; Berger, Amanda ; Gonzalez-Escobedo, Geoffrey ; Mandlik, Anjali ; Bhuiyan, Taufiqur Rahman ; Leung, Daniel T ; LaRocque, Regina C ; Harris, Jason B ; Calderwood, Stephen B ; Qadri, Firdausi ; Vann, W F ; Kováč, Pavol ; Ryan, Edward T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-f05dc21cca877688976d0f7162c8db1a7eea8d29564329122472c8b3dc393b433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Animals</topic><topic>Antibodies, Bacterial - 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Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS).
Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization.
Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.
We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26154421</pmid><doi>10.1371/journal.pntd.0003881</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | PLoS neglected tropical diseases, 2015-07, Vol.9 (7), p.e0003881 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1720468965 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Adolescent Adult Age Animals Antibodies, Bacterial - immunology Bacteriology Child Child, Preschool Cholera Cholera - immunology Cholera - microbiology Cholera - prevention & control Cholera Vaccines - administration & dosage Cholera Vaccines - chemistry Cholera Vaccines - immunology Disease Models, Animal Female Humans Immunization Immunologic Memory Infections Male Mice Middle Aged Mucous Membrane - immunology O Antigens - administration & dosage O Antigens - genetics O Antigens - immunology Public health Sanitation Tetanus Tetanus Toxin - administration & dosage Tetanus Toxin - chemistry Tetanus Toxin - immunology Vaccines Vaccines, Conjugate - administration & dosage Vaccines, Conjugate - chemistry Vaccines, Conjugate - immunology Vibrio cholerae O1 - immunology Young Adult |
| title | A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T20%3A16%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Cholera%20Conjugate%20Vaccine%20Containing%20O-specific%20Polysaccharide%20(OSP)%20of%20V.%20cholerae%20O1%20Inaba%20and%20Recombinant%20Fragment%20of%20Tetanus%20Toxin%20Heavy%20Chain%20(OSP:rTTHc)%20Induces%20Serum,%20Memory%20and%20Lamina%20Proprial%20Responses%20against%20OSP%20and%20Is%20Protective%20in%20Mice&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Sayeed,%20Md%20Abu&rft.date=2015-07-08&rft.volume=9&rft.issue=7&rft.spage=e0003881&rft.pages=e0003881-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0003881&rft_dat=%3Cproquest_plos_%3E1709166617%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1709166617&rft_id=info:pmid/26154421&rft_doaj_id=oai_doaj_org_article_0e79629c217d48a793da67a0f610ed0b&rfr_iscdi=true |