On technological and immunological benefits of multivalent single-injection microsphere vaccines
With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. Mono- and mu...
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| Veröffentlicht in: | Pharmaceutical research 2002-09, Vol.19 (9), p.1330-1336 |
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| creator | BOEHM, Gérard PEYRE, Marisa SESARDIC, Dorothea HUSKISSON, Rachel J MAWAS, Fatme DOUGLAS, Alexandra XING, Dorothy MERKLE, Hans P GANDER, Bruno JOHANSEN, Pal |
| description | With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity.
Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs.
Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs.
This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components. |
| doi_str_mv | 10.1023/a:1020354809581 |
| format | Article |
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Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs.
Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs.
This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1023/a:1020354809581</identifier><identifier>PMID: 12403070</identifier><identifier>CODEN: PHREEB</identifier><language>eng</language><publisher>New York, NY: Springer</publisher><subject>Animals ; Antigens ; Biological and medical sciences ; Cellulose acetate ; Efficiency ; Female ; General pharmacology ; Guinea Pigs ; Hypotheses ; Immunology ; Immunomodulators ; Injections, Subcutaneous ; Medical sciences ; Microspheres ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Proteins ; Tetanus ; Vaccines ; Vaccines - administration & dosage ; Vaccines - immunology ; Whooping cough</subject><ispartof>Pharmaceutical research, 2002-09, Vol.19 (9), p.1330-1336</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Kluwer Academic Publishers Sep 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-7b0fb22508e02f72460cada8383c1f8f6167cb00b9d9ce072326889c343b2aed3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13978332$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12403070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BOEHM, Gérard</creatorcontrib><creatorcontrib>PEYRE, Marisa</creatorcontrib><creatorcontrib>SESARDIC, Dorothea</creatorcontrib><creatorcontrib>HUSKISSON, Rachel J</creatorcontrib><creatorcontrib>MAWAS, Fatme</creatorcontrib><creatorcontrib>DOUGLAS, Alexandra</creatorcontrib><creatorcontrib>XING, Dorothy</creatorcontrib><creatorcontrib>MERKLE, Hans P</creatorcontrib><creatorcontrib>GANDER, Bruno</creatorcontrib><creatorcontrib>JOHANSEN, Pal</creatorcontrib><title>On technological and immunological benefits of multivalent single-injection microsphere vaccines</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity.
Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs.
Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs.
This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.</description><subject>Animals</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Cellulose acetate</subject><subject>Efficiency</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Guinea Pigs</subject><subject>Hypotheses</subject><subject>Immunology</subject><subject>Immunomodulators</subject><subject>Injections, Subcutaneous</subject><subject>Medical sciences</subject><subject>Microspheres</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Proteins</subject><subject>Tetanus</subject><subject>Vaccines</subject><subject>Vaccines - administration & dosage</subject><subject>Vaccines - immunology</subject><subject>Whooping cough</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpd0E1Lw0AQBuBFFK3VszcJgt6isx_JbrxJ8QsKvSh4i5vNbLtls6nZpOC_N2Cl4GlgeBjeeQm5oHBLgfE7fT8O4JlQUGSKHpAJzSRPCxAfh2QCkolUSUFPyGmMawBQtBDH5IQyARwkTMjnIiQ9mlVofbt0RvtEhzpxTTPsNxUGtK6PSWuTZvC922qPoU-iC0uPqQtrNL1rQ9I407Vxs8IOk602xgWMZ-TIah_xfDen5P3p8W32ks4Xz6-zh3lqBJV9KiuwFWMZKARmx9w5GF1rxRU31Cqb01yaCqAq6sLg-BhnuVKF4YJXTGPNp-Tm9-6ma78GjH3ZuGjQex2wHWIpWc6pojDCq39w3Q5dGLOVjAHloJQa0eUODVWDdbnpXKO77_KvuBFc74COY0e208G4uHe8kIpzxn8ARVR9Rw</recordid><startdate>20020901</startdate><enddate>20020901</enddate><creator>BOEHM, Gérard</creator><creator>PEYRE, Marisa</creator><creator>SESARDIC, Dorothea</creator><creator>HUSKISSON, Rachel J</creator><creator>MAWAS, Fatme</creator><creator>DOUGLAS, Alexandra</creator><creator>XING, Dorothy</creator><creator>MERKLE, Hans P</creator><creator>GANDER, Bruno</creator><creator>JOHANSEN, Pal</creator><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20020901</creationdate><title>On technological and immunological benefits of multivalent single-injection microsphere vaccines</title><author>BOEHM, Gérard ; PEYRE, Marisa ; SESARDIC, Dorothea ; HUSKISSON, Rachel J ; MAWAS, Fatme ; DOUGLAS, Alexandra ; XING, Dorothy ; MERKLE, Hans P ; GANDER, Bruno ; JOHANSEN, Pal</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-7b0fb22508e02f72460cada8383c1f8f6167cb00b9d9ce072326889c343b2aed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Cellulose acetate</topic><topic>Efficiency</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Guinea Pigs</topic><topic>Hypotheses</topic><topic>Immunology</topic><topic>Immunomodulators</topic><topic>Injections, Subcutaneous</topic><topic>Medical sciences</topic><topic>Microspheres</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Proteins</topic><topic>Tetanus</topic><topic>Vaccines</topic><topic>Vaccines - administration & dosage</topic><topic>Vaccines - immunology</topic><topic>Whooping cough</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BOEHM, Gérard</creatorcontrib><creatorcontrib>PEYRE, Marisa</creatorcontrib><creatorcontrib>SESARDIC, Dorothea</creatorcontrib><creatorcontrib>HUSKISSON, Rachel J</creatorcontrib><creatorcontrib>MAWAS, Fatme</creatorcontrib><creatorcontrib>DOUGLAS, Alexandra</creatorcontrib><creatorcontrib>XING, Dorothy</creatorcontrib><creatorcontrib>MERKLE, Hans P</creatorcontrib><creatorcontrib>GANDER, Bruno</creatorcontrib><creatorcontrib>JOHANSEN, Pal</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & 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>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BOEHM, Gérard</au><au>PEYRE, Marisa</au><au>SESARDIC, Dorothea</au><au>HUSKISSON, Rachel J</au><au>MAWAS, Fatme</au><au>DOUGLAS, Alexandra</au><au>XING, Dorothy</au><au>MERKLE, Hans P</au><au>GANDER, Bruno</au><au>JOHANSEN, Pal</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>On technological and immunological benefits of multivalent single-injection microsphere vaccines</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2002-09-01</date><risdate>2002</risdate><volume>19</volume><issue>9</issue><spage>1330</spage><epage>1336</epage><pages>1330-1336</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><coden>PHREEB</coden><abstract>With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity.
Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs.
Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs.
This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.</abstract><cop>New York, NY</cop><pub>Springer</pub><pmid>12403070</pmid><doi>10.1023/a:1020354809581</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens Biological and medical sciences Cellulose acetate Efficiency Female General pharmacology Guinea Pigs Hypotheses Immunology Immunomodulators Injections, Subcutaneous Medical sciences Microspheres Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Proteins Tetanus Vaccines Vaccines - administration & dosage Vaccines - immunology Whooping cough |
| title | On technological and immunological benefits of multivalent single-injection microsphere vaccines |
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