Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230
Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of...
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| Veröffentlicht in: | Vaccine 2020-07, Vol.38 (34), p.5480-5489 |
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| creator | Scaria, Puthupparampil V. Chen, Beth B. Rowe, Christopher G. Alani, Nada Muratova, Olga V. Barnafo, Emma K. Lambert, Lynn E. Zaidi, Irfan U. Lees, Andrew Rausch, Kelly M. Narum, David L. Duffy, Patrick E. |
| description | Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials. Nonetheless, more potent carriers may augment the immunogenicity of these antigens for a more efficacious vaccine; here, we evaluate a series of proteins to identify such a carrier. Pfs25 and Pfs230 were chemically conjugated to 4 different carriers [tetanus toxoid (TT), a recombinant fragment of tetanus toxin heavy chain (rTThc), recombinant CRM197 produced in Pseudomonas fluorescens (CRM197) or in E. coli (EcoCRM®)] and compared to EPA conjugates in mouse immunogenicity studies. Conjugates of each antigen formulated in Alhydrogel® elicited similar antibody titers but showed differences in functional activity. At a 0.5 µg dose, Pfs230 conjugated to TT, CRM197 and EcoCRM® showed significantly higher functional activity compared to EPA. When formulated with the more potent adjuvant GLA-LSQ, all 4 alternate conjugates induced higher antibody titers as well as increased functional activity compared to the EPA conjugate. IgG subclass analysis of Pfs230 conjugates showed no carrier-dependent differences in the IgG profile. While Alhydrogel® formulations induced a Th2 dominant immune response, GLA-LSQ formulations induced a mixed Th1/Th2 response. |
| doi_str_mv | 10.1016/j.vaccine.2020.06.018 |
| format | Article |
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Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials. Nonetheless, more potent carriers may augment the immunogenicity of these antigens for a more efficacious vaccine; here, we evaluate a series of proteins to identify such a carrier. Pfs25 and Pfs230 were chemically conjugated to 4 different carriers [tetanus toxoid (TT), a recombinant fragment of tetanus toxin heavy chain (rTThc), recombinant CRM197 produced in Pseudomonas fluorescens (CRM197) or in E. coli (EcoCRM®)] and compared to EPA conjugates in mouse immunogenicity studies. Conjugates of each antigen formulated in Alhydrogel® elicited similar antibody titers but showed differences in functional activity. At a 0.5 µg dose, Pfs230 conjugated to TT, CRM197 and EcoCRM® showed significantly higher functional activity compared to EPA. When formulated with the more potent adjuvant GLA-LSQ, all 4 alternate conjugates induced higher antibody titers as well as increased functional activity compared to the EPA conjugate. IgG subclass analysis of Pfs230 conjugates showed no carrier-dependent differences in the IgG profile. While Alhydrogel® formulations induced a Th2 dominant immune response, GLA-LSQ formulations induced a mixed Th1/Th2 response.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2020.06.018</identifier><identifier>PMID: 32600913</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Amino acids ; Animals ; Antibodies ; Antibodies, Protozoan ; Antigens ; Antigens, Protozoan ; Bacterial infections ; Carrier protein ; Carrier Proteins ; Chromatography ; Clinical trials ; Conjugates ; Conjugation ; Disease transmission ; E coli ; Escherichia coli - metabolism ; Immune response ; Immune system ; Immunization ; Immunogenicity ; Immunoglobulin G ; Infections ; Infectious diseases ; Lymphocytes T ; Malaria ; Malaria Vaccines ; Malaria, Falciparum - prevention & control ; Mice ; Mosquitoes ; Parasites ; Pfs230 ; Pfs25 ; Plasmodium falciparum ; Proteins ; Protozoan Proteins - metabolism ; Pseudomonas fluorescens ; Tetanus ; Tetanus toxin ; Toxins ; Transmission-blocking vaccine ; Vaccines ; Vector-borne diseases</subject><ispartof>Vaccine, 2020-07, Vol.38 (34), p.5480-5489</ispartof><rights>2020</rights><rights>Published by Elsevier Ltd.</rights><rights>Copyright Elsevier Limited Jul 22, 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-da20aecd23b11e220bad4dfd3f0a3d301c458007311b729fadf41b2e32c154873</citedby><cites>FETCH-LOGICAL-c393t-da20aecd23b11e220bad4dfd3f0a3d301c458007311b729fadf41b2e32c154873</cites><orcidid>0000-0002-8370-4876 ; 0000-0003-3041-5402 ; 0000-0002-4483-5005</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X20307908$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32600913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scaria, Puthupparampil V.</creatorcontrib><creatorcontrib>Chen, Beth B.</creatorcontrib><creatorcontrib>Rowe, Christopher G.</creatorcontrib><creatorcontrib>Alani, Nada</creatorcontrib><creatorcontrib>Muratova, Olga V.</creatorcontrib><creatorcontrib>Barnafo, Emma K.</creatorcontrib><creatorcontrib>Lambert, Lynn E.</creatorcontrib><creatorcontrib>Zaidi, Irfan U.</creatorcontrib><creatorcontrib>Lees, Andrew</creatorcontrib><creatorcontrib>Rausch, Kelly M.</creatorcontrib><creatorcontrib>Narum, David L.</creatorcontrib><creatorcontrib>Duffy, Patrick E.</creatorcontrib><title>Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials. Nonetheless, more potent carriers may augment the immunogenicity of these antigens for a more efficacious vaccine; here, we evaluate a series of proteins to identify such a carrier. Pfs25 and Pfs230 were chemically conjugated to 4 different carriers [tetanus toxoid (TT), a recombinant fragment of tetanus toxin heavy chain (rTThc), recombinant CRM197 produced in Pseudomonas fluorescens (CRM197) or in E. coli (EcoCRM®)] and compared to EPA conjugates in mouse immunogenicity studies. Conjugates of each antigen formulated in Alhydrogel® elicited similar antibody titers but showed differences in functional activity. At a 0.5 µg dose, Pfs230 conjugated to TT, CRM197 and EcoCRM® showed significantly higher functional activity compared to EPA. When formulated with the more potent adjuvant GLA-LSQ, all 4 alternate conjugates induced higher antibody titers as well as increased functional activity compared to the EPA conjugate. IgG subclass analysis of Pfs230 conjugates showed no carrier-dependent differences in the IgG profile. While Alhydrogel® formulations induced a Th2 dominant immune response, GLA-LSQ formulations induced a mixed Th1/Th2 response.</description><subject>Amino acids</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Protozoan</subject><subject>Antigens</subject><subject>Antigens, Protozoan</subject><subject>Bacterial infections</subject><subject>Carrier protein</subject><subject>Carrier Proteins</subject><subject>Chromatography</subject><subject>Clinical trials</subject><subject>Conjugates</subject><subject>Conjugation</subject><subject>Disease transmission</subject><subject>E coli</subject><subject>Escherichia coli - metabolism</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Lymphocytes T</subject><subject>Malaria</subject><subject>Malaria Vaccines</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Mice</subject><subject>Mosquitoes</subject><subject>Parasites</subject><subject>Pfs230</subject><subject>Pfs25</subject><subject>Plasmodium falciparum</subject><subject>Proteins</subject><subject>Protozoan Proteins - metabolism</subject><subject>Pseudomonas fluorescens</subject><subject>Tetanus</subject><subject>Tetanus toxin</subject><subject>Toxins</subject><subject>Transmission-blocking vaccine</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU-LFDEQxYMo7uzqR1ACXjzYbVXSf08ig67Cgh4UvIV0Uj2k7U7GpHvBb2_GGT148ZQEfq9S7z3GniGUCNi8nsp7bYzzVAoQUEJTAnYP2A67Vhaixu4h24FoqqJC-HbFrlOaAKCW2D9mV1I0AD3KHZv3YTnq6FLwPIzc6BgdRX6MYSXnE18DN8FP20GvxBc9Z1TzNWqfFpeSy6phDua78wd-2Ydrv7oD-fSKfx6TqPPb_r5JeMIejXpO9PRy3rCv79992X8o7j7dfty_vSuM7OVaWC1Ak7FCDogkBAzaVna0cgQtrQQ0Vd0BtBJxaEU_ajtWOAiSwmBdZf837OV5brbxY6O0qrysoXnWnsKWlKiwh65BOKEv_kGnsEWft8uUEC22lWwyVZ8pE0NKkUZ1jG7R8adCUKc61KQu9tWpDgWNynVk3fPL9G1YyP5V_ck_A2_OAOU47nPyKhlH3pB1kcyqbHD_-eIXH7Gd8w</recordid><startdate>20200722</startdate><enddate>20200722</enddate><creator>Scaria, Puthupparampil V.</creator><creator>Chen, Beth B.</creator><creator>Rowe, Christopher G.</creator><creator>Alani, Nada</creator><creator>Muratova, Olga V.</creator><creator>Barnafo, Emma K.</creator><creator>Lambert, Lynn E.</creator><creator>Zaidi, Irfan U.</creator><creator>Lees, Andrew</creator><creator>Rausch, Kelly M.</creator><creator>Narum, David L.</creator><creator>Duffy, Patrick E.</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>AEUYN</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><orcidid>https://orcid.org/0000-0002-8370-4876</orcidid><orcidid>https://orcid.org/0000-0003-3041-5402</orcidid><orcidid>https://orcid.org/0000-0002-4483-5005</orcidid></search><sort><creationdate>20200722</creationdate><title>Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230</title><author>Scaria, Puthupparampil V. ; Chen, Beth B. ; Rowe, Christopher G. ; Alani, Nada ; Muratova, Olga V. ; Barnafo, Emma K. ; Lambert, Lynn E. ; Zaidi, Irfan U. ; Lees, Andrew ; Rausch, Kelly M. ; Narum, David L. ; Duffy, Patrick E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-da20aecd23b11e220bad4dfd3f0a3d301c458007311b729fadf41b2e32c154873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Amino acids</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Protozoan</topic><topic>Antigens</topic><topic>Antigens, Protozoan</topic><topic>Bacterial infections</topic><topic>Carrier protein</topic><topic>Carrier Proteins</topic><topic>Chromatography</topic><topic>Clinical trials</topic><topic>Conjugates</topic><topic>Conjugation</topic><topic>Disease transmission</topic><topic>E coli</topic><topic>Escherichia coli - 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Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scaria, Puthupparampil V.</au><au>Chen, Beth B.</au><au>Rowe, Christopher G.</au><au>Alani, Nada</au><au>Muratova, Olga V.</au><au>Barnafo, Emma K.</au><au>Lambert, Lynn E.</au><au>Zaidi, Irfan U.</au><au>Lees, Andrew</au><au>Rausch, Kelly M.</au><au>Narum, David L.</au><au>Duffy, Patrick E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2020-07-22</date><risdate>2020</risdate><volume>38</volume><issue>34</issue><spage>5480</spage><epage>5489</epage><pages>5480-5489</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials. Nonetheless, more potent carriers may augment the immunogenicity of these antigens for a more efficacious vaccine; here, we evaluate a series of proteins to identify such a carrier. Pfs25 and Pfs230 were chemically conjugated to 4 different carriers [tetanus toxoid (TT), a recombinant fragment of tetanus toxin heavy chain (rTThc), recombinant CRM197 produced in Pseudomonas fluorescens (CRM197) or in E. coli (EcoCRM®)] and compared to EPA conjugates in mouse immunogenicity studies. Conjugates of each antigen formulated in Alhydrogel® elicited similar antibody titers but showed differences in functional activity. At a 0.5 µg dose, Pfs230 conjugated to TT, CRM197 and EcoCRM® showed significantly higher functional activity compared to EPA. When formulated with the more potent adjuvant GLA-LSQ, all 4 alternate conjugates induced higher antibody titers as well as increased functional activity compared to the EPA conjugate. IgG subclass analysis of Pfs230 conjugates showed no carrier-dependent differences in the IgG profile. While Alhydrogel® formulations induced a Th2 dominant immune response, GLA-LSQ formulations induced a mixed Th1/Th2 response.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>32600913</pmid><doi>10.1016/j.vaccine.2020.06.018</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8370-4876</orcidid><orcidid>https://orcid.org/0000-0003-3041-5402</orcidid><orcidid>https://orcid.org/0000-0002-4483-5005</orcidid></addata></record> |
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| ispartof | Vaccine, 2020-07, Vol.38 (34), p.5480-5489 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino acids Animals Antibodies Antibodies, Protozoan Antigens Antigens, Protozoan Bacterial infections Carrier protein Carrier Proteins Chromatography Clinical trials Conjugates Conjugation Disease transmission E coli Escherichia coli - metabolism Immune response Immune system Immunization Immunogenicity Immunoglobulin G Infections Infectious diseases Lymphocytes T Malaria Malaria Vaccines Malaria, Falciparum - prevention & control Mice Mosquitoes Parasites Pfs230 Pfs25 Plasmodium falciparum Proteins Protozoan Proteins - metabolism Pseudomonas fluorescens Tetanus Tetanus toxin Toxins Transmission-blocking vaccine Vaccines Vector-borne diseases |
| title | Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230 |
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