Loading…

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bo...

Full description

Saved in:
Bibliographic Details
Published in:Vaccine 2015-02, Vol.33 (6), p.783-788
Main Authors: Kothari, Neha, Kothari, Sudeep, Choi, Young Joo, Dey, Ayan, Briles, David E, Rhee, Dong Kwon, Carbis, Rodney
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23
cites cdi_FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23
container_end_page 788
container_issue 6
container_start_page 783
container_title Vaccine
container_volume 33
creator Kothari, Neha
Kothari, Sudeep
Choi, Young Joo
Dey, Ayan
Briles, David E
Rhee, Dong Kwon
Carbis, Rodney
description Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae . Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.
doi_str_mv 10.1016/j.vaccine.2014.12.032
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1654696751</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0264410X14016855</els_id><sourcerecordid>1654696751</sourcerecordid><originalsourceid>FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23</originalsourceid><addsrcrecordid>eNqNks-qEzEUxoMo3lp9BCXgxs3UJJNkZjZKufgPLij0Cu5CJnOmTZ0mY5Kp9I18TDO2KtyNrg45fN-XnPwOQk8pWVFC5cv96qiNsQ5WjFC-omxFSnYPLWhdlQUTtL6PFoRJXnBKvlyhRzHuCSGipM1DdMWE4EI05QL9WOPWHvUALmHj3X7a6gT4Ej13krbOui3-FMc17vXBDhYipli7DjO80xGnHeDRp5xg9YCTx2PIJ5Ow3mZvzBV_tx3goN0WsO_xJgUYkzfemCni0cF08M5qwDGF2fEre6OH3IVh0Pj2NO7sY_Sg10OEJ5e6RJ_fvrm9fl_cfHz34Xp9UxghaCp4RwVtObRARdNXvKwrLnndGs4FAWlkJeuaNL0oOek0B5C8aZhuoQYBxLByiV6cc_MU3yaISR1sNPM7HPgpKioFl42sBP0fKeOkkqXM0ud3pHs_BZcHySpek6oRmdsSibPKBB9jgF6NwR50OClK1Exd7dUFjZqpK8pUpp59zy7pU3uA7o_rN-YseH0WQP65o4WgorHgDHQ2ZFKq8_afV7y6k2CGvBhGD1_hBPHvNCpmg9rMqzdvHuU5sxai_AnvrNZJ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1648079587</pqid></control><display><type>article</type><title>A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi</title><source>ScienceDirect Journals</source><creator>Kothari, Neha ; Kothari, Sudeep ; Choi, Young Joo ; Dey, Ayan ; Briles, David E ; Rhee, Dong Kwon ; Carbis, Rodney</creator><creatorcontrib>Kothari, Neha ; Kothari, Sudeep ; Choi, Young Joo ; Dey, Ayan ; Briles, David E ; Rhee, Dong Kwon ; Carbis, Rodney</creatorcontrib><description>Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae . Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2014.12.032</identifier><identifier>PMID: 25545593</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animals ; Antibodies, Bacterial - biosynthesis ; Antibodies, Bacterial - blood ; Antigens ; Bacteria ; Bacterial Proteins - chemistry ; Bacterial Proteins - classification ; Bacterial Proteins - immunology ; Binding sites ; Cross Protection ; Cross Reactions ; Cytokines ; Female ; Gram-positive bacteria ; Immune response ; Immunoconjugates - chemistry ; Immunoconjugates - immunology ; Immunoglobulin Class Switching ; Immunoglobulin G - biosynthesis ; Immunoglobulin G - blood ; Mice ; Mice, Inbred ICR ; Pneumococcal Infections - blood ; Pneumococcal Infections - immunology ; Pneumococcal Infections - mortality ; Pneumococcal Infections - prevention &amp; control ; Pneumococcal Vaccines - administration &amp; dosage ; Pneumococcal Vaccines - chemical synthesis ; Pneumococcal Vaccines - immunology ; Polysaccharides, Bacterial - chemistry ; Polysaccharides, Bacterial - immunology ; Proteins ; Salmonella Typhi ; Salmonella typhi - drug effects ; Salmonella typhi - immunology ; Streptococcus infections ; Streptococcus pneumoniae ; Streptococcus pneumoniae - drug effects ; Streptococcus pneumoniae - immunology ; Survival Analysis ; Th1-Th2 Balance ; Typhoid Fever - blood ; Typhoid Fever - immunology ; Typhoid Fever - mortality ; Typhoid Fever - prevention &amp; control ; Typhoid-Paratyphoid Vaccines - administration &amp; dosage ; Typhoid-Paratyphoid Vaccines - chemical synthesis ; Typhoid-Paratyphoid Vaccines - immunology ; Vaccine development ; Vaccines ; Vaccines, Conjugate ; Vi-PspA conjugate vaccine</subject><ispartof>Vaccine, 2015-02, Vol.33 (6), p.783-788</ispartof><rights>Elsevier Ltd</rights><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 4, 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23</citedby><cites>FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25545593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kothari, Neha</creatorcontrib><creatorcontrib>Kothari, Sudeep</creatorcontrib><creatorcontrib>Choi, Young Joo</creatorcontrib><creatorcontrib>Dey, Ayan</creatorcontrib><creatorcontrib>Briles, David E</creatorcontrib><creatorcontrib>Rhee, Dong Kwon</creatorcontrib><creatorcontrib>Carbis, Rodney</creatorcontrib><title>A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae . Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antibodies, Bacterial - biosynthesis</subject><subject>Antibodies, Bacterial - blood</subject><subject>Antigens</subject><subject>Bacteria</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - classification</subject><subject>Bacterial Proteins - immunology</subject><subject>Binding sites</subject><subject>Cross Protection</subject><subject>Cross Reactions</subject><subject>Cytokines</subject><subject>Female</subject><subject>Gram-positive bacteria</subject><subject>Immune response</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunoconjugates - immunology</subject><subject>Immunoglobulin Class Switching</subject><subject>Immunoglobulin G - biosynthesis</subject><subject>Immunoglobulin G - blood</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Pneumococcal Infections - blood</subject><subject>Pneumococcal Infections - immunology</subject><subject>Pneumococcal Infections - mortality</subject><subject>Pneumococcal Infections - prevention &amp; control</subject><subject>Pneumococcal Vaccines - administration &amp; dosage</subject><subject>Pneumococcal Vaccines - chemical synthesis</subject><subject>Pneumococcal Vaccines - immunology</subject><subject>Polysaccharides, Bacterial - chemistry</subject><subject>Polysaccharides, Bacterial - immunology</subject><subject>Proteins</subject><subject>Salmonella Typhi</subject><subject>Salmonella typhi - drug effects</subject><subject>Salmonella typhi - immunology</subject><subject>Streptococcus infections</subject><subject>Streptococcus pneumoniae</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Streptococcus pneumoniae - immunology</subject><subject>Survival Analysis</subject><subject>Th1-Th2 Balance</subject><subject>Typhoid Fever - blood</subject><subject>Typhoid Fever - immunology</subject><subject>Typhoid Fever - mortality</subject><subject>Typhoid Fever - prevention &amp; control</subject><subject>Typhoid-Paratyphoid Vaccines - administration &amp; dosage</subject><subject>Typhoid-Paratyphoid Vaccines - chemical synthesis</subject><subject>Typhoid-Paratyphoid Vaccines - immunology</subject><subject>Vaccine development</subject><subject>Vaccines</subject><subject>Vaccines, Conjugate</subject><subject>Vi-PspA conjugate vaccine</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqNks-qEzEUxoMo3lp9BCXgxs3UJJNkZjZKufgPLij0Cu5CJnOmTZ0mY5Kp9I18TDO2KtyNrg45fN-XnPwOQk8pWVFC5cv96qiNsQ5WjFC-omxFSnYPLWhdlQUTtL6PFoRJXnBKvlyhRzHuCSGipM1DdMWE4EI05QL9WOPWHvUALmHj3X7a6gT4Ej13krbOui3-FMc17vXBDhYipli7DjO80xGnHeDRp5xg9YCTx2PIJ5Ow3mZvzBV_tx3goN0WsO_xJgUYkzfemCni0cF08M5qwDGF2fEre6OH3IVh0Pj2NO7sY_Sg10OEJ5e6RJ_fvrm9fl_cfHz34Xp9UxghaCp4RwVtObRARdNXvKwrLnndGs4FAWlkJeuaNL0oOek0B5C8aZhuoQYBxLByiV6cc_MU3yaISR1sNPM7HPgpKioFl42sBP0fKeOkkqXM0ud3pHs_BZcHySpek6oRmdsSibPKBB9jgF6NwR50OClK1Exd7dUFjZqpK8pUpp59zy7pU3uA7o_rN-YseH0WQP65o4WgorHgDHQ2ZFKq8_afV7y6k2CGvBhGD1_hBPHvNCpmg9rMqzdvHuU5sxai_AnvrNZJ</recordid><startdate>20150204</startdate><enddate>20150204</enddate><creator>Kothari, Neha</creator><creator>Kothari, Sudeep</creator><creator>Choi, Young Joo</creator><creator>Dey, Ayan</creator><creator>Briles, David E</creator><creator>Rhee, Dong Kwon</creator><creator>Carbis, Rodney</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20150204</creationdate><title>A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi</title><author>Kothari, Neha ; Kothari, Sudeep ; Choi, Young Joo ; Dey, Ayan ; Briles, David E ; Rhee, Dong Kwon ; Carbis, Rodney</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antibodies, Bacterial - biosynthesis</topic><topic>Antibodies, Bacterial - blood</topic><topic>Antigens</topic><topic>Bacteria</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - classification</topic><topic>Bacterial Proteins - immunology</topic><topic>Binding sites</topic><topic>Cross Protection</topic><topic>Cross Reactions</topic><topic>Cytokines</topic><topic>Female</topic><topic>Gram-positive bacteria</topic><topic>Immune response</topic><topic>Immunoconjugates - chemistry</topic><topic>Immunoconjugates - immunology</topic><topic>Immunoglobulin Class Switching</topic><topic>Immunoglobulin G - biosynthesis</topic><topic>Immunoglobulin G - blood</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Pneumococcal Infections - blood</topic><topic>Pneumococcal Infections - immunology</topic><topic>Pneumococcal Infections - mortality</topic><topic>Pneumococcal Infections - prevention &amp; control</topic><topic>Pneumococcal Vaccines - administration &amp; dosage</topic><topic>Pneumococcal Vaccines - chemical synthesis</topic><topic>Pneumococcal Vaccines - immunology</topic><topic>Polysaccharides, Bacterial - chemistry</topic><topic>Polysaccharides, Bacterial - immunology</topic><topic>Proteins</topic><topic>Salmonella Typhi</topic><topic>Salmonella typhi - drug effects</topic><topic>Salmonella typhi - immunology</topic><topic>Streptococcus infections</topic><topic>Streptococcus pneumoniae</topic><topic>Streptococcus pneumoniae - drug effects</topic><topic>Streptococcus pneumoniae - immunology</topic><topic>Survival Analysis</topic><topic>Th1-Th2 Balance</topic><topic>Typhoid Fever - blood</topic><topic>Typhoid Fever - immunology</topic><topic>Typhoid Fever - mortality</topic><topic>Typhoid Fever - prevention &amp; control</topic><topic>Typhoid-Paratyphoid Vaccines - administration &amp; dosage</topic><topic>Typhoid-Paratyphoid Vaccines - chemical synthesis</topic><topic>Typhoid-Paratyphoid Vaccines - immunology</topic><topic>Vaccine development</topic><topic>Vaccines</topic><topic>Vaccines, Conjugate</topic><topic>Vi-PspA conjugate vaccine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kothari, Neha</creatorcontrib><creatorcontrib>Kothari, Sudeep</creatorcontrib><creatorcontrib>Choi, Young Joo</creatorcontrib><creatorcontrib>Dey, Ayan</creatorcontrib><creatorcontrib>Briles, David E</creatorcontrib><creatorcontrib>Rhee, Dong Kwon</creatorcontrib><creatorcontrib>Carbis, Rodney</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest - Health &amp; Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>ProQuest Health Management</collection><collection>Medical Database</collection><collection>ProQuest_Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kothari, Neha</au><au>Kothari, Sudeep</au><au>Choi, Young Joo</au><au>Dey, Ayan</au><au>Briles, David E</au><au>Rhee, Dong Kwon</au><au>Carbis, Rodney</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2015-02-04</date><risdate>2015</risdate><volume>33</volume><issue>6</issue><spage>783</spage><epage>788</epage><pages>783-788</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>Abstract Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae . Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the α helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the α helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>25545593</pmid><doi>10.1016/j.vaccine.2014.12.032</doi><tpages>6</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0264-410X
ispartof Vaccine, 2015-02, Vol.33 (6), p.783-788
issn 0264-410X
1873-2518
language eng
recordid cdi_proquest_miscellaneous_1654696751
source ScienceDirect Journals
subjects Allergy and Immunology
Animals
Antibodies, Bacterial - biosynthesis
Antibodies, Bacterial - blood
Antigens
Bacteria
Bacterial Proteins - chemistry
Bacterial Proteins - classification
Bacterial Proteins - immunology
Binding sites
Cross Protection
Cross Reactions
Cytokines
Female
Gram-positive bacteria
Immune response
Immunoconjugates - chemistry
Immunoconjugates - immunology
Immunoglobulin Class Switching
Immunoglobulin G - biosynthesis
Immunoglobulin G - blood
Mice
Mice, Inbred ICR
Pneumococcal Infections - blood
Pneumococcal Infections - immunology
Pneumococcal Infections - mortality
Pneumococcal Infections - prevention & control
Pneumococcal Vaccines - administration & dosage
Pneumococcal Vaccines - chemical synthesis
Pneumococcal Vaccines - immunology
Polysaccharides, Bacterial - chemistry
Polysaccharides, Bacterial - immunology
Proteins
Salmonella Typhi
Salmonella typhi - drug effects
Salmonella typhi - immunology
Streptococcus infections
Streptococcus pneumoniae
Streptococcus pneumoniae - drug effects
Streptococcus pneumoniae - immunology
Survival Analysis
Th1-Th2 Balance
Typhoid Fever - blood
Typhoid Fever - immunology
Typhoid Fever - mortality
Typhoid Fever - prevention & control
Typhoid-Paratyphoid Vaccines - administration & dosage
Typhoid-Paratyphoid Vaccines - chemical synthesis
Typhoid-Paratyphoid Vaccines - immunology
Vaccine development
Vaccines
Vaccines, Conjugate
Vi-PspA conjugate vaccine
title A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T09%3A26%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20bivalent%20conjugate%20vaccine%20containing%20PspA%20families%201%20and%202%20has%20the%20potential%20to%20protect%20against%20a%20wide%20range%20of%20Streptococcus%20pneumoniae%20strains%20and%20Salmonella%20Typhi&rft.jtitle=Vaccine&rft.au=Kothari,%20Neha&rft.date=2015-02-04&rft.volume=33&rft.issue=6&rft.spage=783&rft.epage=788&rft.pages=783-788&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2014.12.032&rft_dat=%3Cproquest_cross%3E1654696751%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c551t-4d151b4ebe159f743874648bc4450e6c6768809f5340da4ee64992abe8e5e0c23%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1648079587&rft_id=info:pmid/25545593&rfr_iscdi=true