Recombinant PreS‐fusion protein vaccine for birch pollen and apple allergy
Background IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome. Methods We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding s...
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| Veröffentlicht in: | Allergy (Copenhagen) 2024-04, Vol.79 (4), p.1001-1017 |
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| creator | Khaitov, Musa Shilovskiy, Igor Valenta, Rudolf Weber, Milena Korneev, Artem Tulaeva, Inna Gattinger, Pia Hage, Marianne Hofer, Gerhard Konradsen, Jon R. Keller, Walter Akinfenwa, Oluwatoyin Poroshina, Alina Ilina, Nataliya Fedenko, Elena Elisyutina, Olga Litovkina, Alla Smolnikov, Evgenii Nikonova, Aleksandra Rybalkin, Sergei Aldobaev, Vladimir Smirnov, Valeriy Shershakova, Nadezhda Petukhova, Olga Kudlay, Dmitriy Shatilov, Artem Timofeeva, Anastasiya Campana, Raffaela Udin, Sergei Skvortsova, Veronica |
| description | Background
IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome.
Methods
We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.
Results
IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV.
Conclusion
The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
We designed a vaccine consisting of peptides derived from IgE epitopes of birch and apple allergens fused with HBV‐derived PreS. Aluminum hydroxide‐adsorbed AB‐PreS induces IgG antibodies specific for Bet v 1, Mal d 1, and HBV. IgG antibodies induced by AB‐PreS inhibit IgE binding of allergic patients IgE to Bet v 1 and Mal d 1 better than extract‐based vaccines. Anti‐PreS IgG may protect against HBV infection.Abbreviations: Ab‐PreS, recombinant protein, consisting of non‐allergenic peptides derived from the IgE binding sites of Bet v 1 and Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier; Bet v 1, major birch pollen allergen; HBV, hepatitis B virus; Ig, immunoglobulin; Mal d 1, cross‐reactive apple allergen; OD, optical density. |
| doi_str_mv | 10.1111/all.15919 |
| format | Article |
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IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome.
Methods
We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.
Results
IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV.
Conclusion
The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
We designed a vaccine consisting of peptides derived from IgE epitopes of birch and apple allergens fused with HBV‐derived PreS. Aluminum hydroxide‐adsorbed AB‐PreS induces IgG antibodies specific for Bet v 1, Mal d 1, and HBV. IgG antibodies induced by AB‐PreS inhibit IgE binding of allergic patients IgE to Bet v 1 and Mal d 1 better than extract‐based vaccines. Anti‐PreS IgG may protect against HBV infection.Abbreviations: Ab‐PreS, recombinant protein, consisting of non‐allergenic peptides derived from the IgE binding sites of Bet v 1 and Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier; Bet v 1, major birch pollen allergen; HBV, hepatitis B virus; Ig, immunoglobulin; Mal d 1, cross‐reactive apple allergen; OD, optical density.</description><identifier>ISSN: 0105-4538</identifier><identifier>ISSN: 1398-9995</identifier><identifier>EISSN: 1398-9995</identifier><identifier>DOI: 10.1111/all.15919</identifier><identifier>PMID: 37855043</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>allergen ; allergen-specific immunotherapy ; Allergens ; Animals ; Antibodies ; Antigens, Plant ; Bet v 1 antigen ; Betula ; birch pollen-associated food allergy syndrome ; Blocking antibodies ; Cell activation ; Enzyme-linked immunosorbent assay ; Escherichia coli ; Food allergies ; Food Hypersensitivity - prevention & control ; Fusion protein ; Humans ; Immunization ; Immunoglobulin E ; Immunoglobulin G ; Immunotherapy ; Inflammation ; Leukocytes (basophilic) ; Mal d 1 antigen ; Malus ; molecular allergy vaccine ; Plant Proteins ; Pollen ; Proteins ; Rabbits ; Recombinant Fusion Proteins ; Vaccines ; Vaccines, Synthetic</subject><ispartof>Allergy (Copenhagen), 2024-04, Vol.79 (4), p.1001-1017</ispartof><rights>2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.</rights><rights>Copyright © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4639-bd29ac9743bbd82057dd2651bfefb38656c3996b0d19bcd03c5133eae25c56053</citedby><cites>FETCH-LOGICAL-c4639-bd29ac9743bbd82057dd2651bfefb38656c3996b0d19bcd03c5133eae25c56053</cites><orcidid>0000-0001-6126-4075 ; 0000-0002-4609-2591 ; 0000-0001-9610-0935 ; 0000-0003-3091-1596 ; 0000-0002-2261-958X ; 0000-0002-8232-6682 ; 0000-0001-5944-3365 ; 0000-0001-6724-8543 ; 0000-0001-6444-6499 ; 0000-0001-5343-4230 ; 0000-0002-4675-8074 ; 0000-0001-9309-9908 ; 0000-0002-0400-2201 ; 0000-0002-2494-3033 ; 0000-0002-3556-969X ; 0000-0002-5021-9276 ; 0000-0003-2815-280X ; 0000-0003-1878-4467 ; 0000-0001-7745-8624 ; 0000-0003-1302-4178 ; 0000-0002-2107-1364 ; 0000-0002-9248-6989 ; 0000-0002-0911-8860 ; 0000-0002-5825-2687 ; 0000-0002-3339-2608 ; 0000-0003-3780-2878 ; 0000-0003-1864-8684 ; 0000-0003-4961-9640 ; 0000-0003-3358-5087 ; 0000-0002-7817-8197</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fall.15919$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fall.15919$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37855043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-223748$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:154055678$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Khaitov, Musa</creatorcontrib><creatorcontrib>Shilovskiy, Igor</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Weber, Milena</creatorcontrib><creatorcontrib>Korneev, Artem</creatorcontrib><creatorcontrib>Tulaeva, Inna</creatorcontrib><creatorcontrib>Gattinger, Pia</creatorcontrib><creatorcontrib>Hage, Marianne</creatorcontrib><creatorcontrib>Hofer, Gerhard</creatorcontrib><creatorcontrib>Konradsen, Jon R.</creatorcontrib><creatorcontrib>Keller, Walter</creatorcontrib><creatorcontrib>Akinfenwa, Oluwatoyin</creatorcontrib><creatorcontrib>Poroshina, Alina</creatorcontrib><creatorcontrib>Ilina, Nataliya</creatorcontrib><creatorcontrib>Fedenko, Elena</creatorcontrib><creatorcontrib>Elisyutina, Olga</creatorcontrib><creatorcontrib>Litovkina, Alla</creatorcontrib><creatorcontrib>Smolnikov, Evgenii</creatorcontrib><creatorcontrib>Nikonova, Aleksandra</creatorcontrib><creatorcontrib>Rybalkin, Sergei</creatorcontrib><creatorcontrib>Aldobaev, Vladimir</creatorcontrib><creatorcontrib>Smirnov, Valeriy</creatorcontrib><creatorcontrib>Shershakova, Nadezhda</creatorcontrib><creatorcontrib>Petukhova, Olga</creatorcontrib><creatorcontrib>Kudlay, Dmitriy</creatorcontrib><creatorcontrib>Shatilov, Artem</creatorcontrib><creatorcontrib>Timofeeva, Anastasiya</creatorcontrib><creatorcontrib>Campana, Raffaela</creatorcontrib><creatorcontrib>Udin, Sergei</creatorcontrib><creatorcontrib>Skvortsova, Veronica</creatorcontrib><title>Recombinant PreS‐fusion protein vaccine for birch pollen and apple allergy</title><title>Allergy (Copenhagen)</title><addtitle>Allergy</addtitle><description>Background
IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome.
Methods
We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.
Results
IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV.
Conclusion
The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
We designed a vaccine consisting of peptides derived from IgE epitopes of birch and apple allergens fused with HBV‐derived PreS. Aluminum hydroxide‐adsorbed AB‐PreS induces IgG antibodies specific for Bet v 1, Mal d 1, and HBV. IgG antibodies induced by AB‐PreS inhibit IgE binding of allergic patients IgE to Bet v 1 and Mal d 1 better than extract‐based vaccines. Anti‐PreS IgG may protect against HBV infection.Abbreviations: Ab‐PreS, recombinant protein, consisting of non‐allergenic peptides derived from the IgE binding sites of Bet v 1 and Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier; Bet v 1, major birch pollen allergen; HBV, hepatitis B virus; Ig, immunoglobulin; Mal d 1, cross‐reactive apple allergen; OD, optical density.</description><subject>allergen</subject><subject>allergen-specific immunotherapy</subject><subject>Allergens</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens, Plant</subject><subject>Bet v 1 antigen</subject><subject>Betula</subject><subject>birch pollen-associated food allergy syndrome</subject><subject>Blocking antibodies</subject><subject>Cell activation</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Escherichia coli</subject><subject>Food allergies</subject><subject>Food Hypersensitivity - prevention & control</subject><subject>Fusion protein</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunoglobulin E</subject><subject>Immunoglobulin G</subject><subject>Immunotherapy</subject><subject>Inflammation</subject><subject>Leukocytes (basophilic)</subject><subject>Mal d 1 antigen</subject><subject>Malus</subject><subject>molecular allergy vaccine</subject><subject>Plant Proteins</subject><subject>Pollen</subject><subject>Proteins</subject><subject>Rabbits</subject><subject>Recombinant Fusion Proteins</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic</subject><issn>0105-4538</issn><issn>1398-9995</issn><issn>1398-9995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1DAUhi0EokNhwQsgS2xAIu2xHSfxclQurRQJxG1r2c5JccnEqT2hmh2PwDP2SXCboQukemPL-vTpP-cn5DmDI5bPsRmGIyYVUw_IignVFEop-ZCsgIEsSimaA_IkpQsAqLmCx-RA1I2UUIoVaT-jCxvrRzNu6aeIX65__-nn5MNIpxi26Ef6yzjnR6R9iNT66H7QKQwDjtSMHTXTNCDNATCe756SR70ZEj7b34fk2_t3X09Oi_bjh7OTdVu4shKqsB1Xxqm6FNZ2DQdZdx2vJLM99lY0laycUKqy0DFlXQfCSSYEGuTSyQqkOCTF4k1XOM1WT9FvTNzpYLzef_3ML9QNl3UNmX9zL__Wf1_rEM91mjXnoi6bjL9a8LyByxnTVm98cjgMZsQwJ82bWpWQA9-YX_6HXoQ5jnl4LYCDKAFUnanXC-ViSClif5eAgb5pUOcF6tsGM_tib5ztBrs78l9lGThegCs_4O5-k1637aL8C-copYg</recordid><startdate>202404</startdate><enddate>202404</enddate><creator>Khaitov, Musa</creator><creator>Shilovskiy, Igor</creator><creator>Valenta, Rudolf</creator><creator>Weber, Milena</creator><creator>Korneev, Artem</creator><creator>Tulaeva, 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PreS‐fusion protein vaccine for birch pollen and apple allergy</title><author>Khaitov, Musa ; Shilovskiy, Igor ; Valenta, Rudolf ; Weber, Milena ; Korneev, Artem ; Tulaeva, Inna ; Gattinger, Pia ; Hage, Marianne ; Hofer, Gerhard ; Konradsen, Jon R. ; Keller, Walter ; Akinfenwa, Oluwatoyin ; Poroshina, Alina ; Ilina, Nataliya ; Fedenko, Elena ; Elisyutina, Olga ; Litovkina, Alla ; Smolnikov, Evgenii ; Nikonova, Aleksandra ; Rybalkin, Sergei ; Aldobaev, Vladimir ; Smirnov, Valeriy ; Shershakova, Nadezhda ; Petukhova, Olga ; Kudlay, Dmitriy ; Shatilov, Artem ; Timofeeva, Anastasiya ; Campana, Raffaela ; Udin, Sergei ; Skvortsova, Veronica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4639-bd29ac9743bbd82057dd2651bfefb38656c3996b0d19bcd03c5133eae25c56053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>allergen</topic><topic>allergen-specific immunotherapy</topic><topic>Allergens</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens, Plant</topic><topic>Bet v 1 antigen</topic><topic>Betula</topic><topic>birch pollen-associated food allergy syndrome</topic><topic>Blocking antibodies</topic><topic>Cell activation</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Escherichia coli</topic><topic>Food allergies</topic><topic>Food Hypersensitivity - prevention & control</topic><topic>Fusion protein</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunoglobulin E</topic><topic>Immunoglobulin G</topic><topic>Immunotherapy</topic><topic>Inflammation</topic><topic>Leukocytes (basophilic)</topic><topic>Mal d 1 antigen</topic><topic>Malus</topic><topic>molecular allergy vaccine</topic><topic>Plant Proteins</topic><topic>Pollen</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Recombinant Fusion Proteins</topic><topic>Vaccines</topic><topic>Vaccines, Synthetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khaitov, Musa</creatorcontrib><creatorcontrib>Shilovskiy, Igor</creatorcontrib><creatorcontrib>Valenta, Rudolf</creatorcontrib><creatorcontrib>Weber, Milena</creatorcontrib><creatorcontrib>Korneev, Artem</creatorcontrib><creatorcontrib>Tulaeva, Inna</creatorcontrib><creatorcontrib>Gattinger, Pia</creatorcontrib><creatorcontrib>Hage, Marianne</creatorcontrib><creatorcontrib>Hofer, Gerhard</creatorcontrib><creatorcontrib>Konradsen, Jon R.</creatorcontrib><creatorcontrib>Keller, Walter</creatorcontrib><creatorcontrib>Akinfenwa, Oluwatoyin</creatorcontrib><creatorcontrib>Poroshina, Alina</creatorcontrib><creatorcontrib>Ilina, Nataliya</creatorcontrib><creatorcontrib>Fedenko, Elena</creatorcontrib><creatorcontrib>Elisyutina, Olga</creatorcontrib><creatorcontrib>Litovkina, Alla</creatorcontrib><creatorcontrib>Smolnikov, Evgenii</creatorcontrib><creatorcontrib>Nikonova, Aleksandra</creatorcontrib><creatorcontrib>Rybalkin, Sergei</creatorcontrib><creatorcontrib>Aldobaev, Vladimir</creatorcontrib><creatorcontrib>Smirnov, Valeriy</creatorcontrib><creatorcontrib>Shershakova, Nadezhda</creatorcontrib><creatorcontrib>Petukhova, Olga</creatorcontrib><creatorcontrib>Kudlay, Dmitriy</creatorcontrib><creatorcontrib>Shatilov, Artem</creatorcontrib><creatorcontrib>Timofeeva, Anastasiya</creatorcontrib><creatorcontrib>Campana, Raffaela</creatorcontrib><creatorcontrib>Udin, Sergei</creatorcontrib><creatorcontrib>Skvortsova, Veronica</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Stockholms universitet</collection><jtitle>Allergy (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khaitov, Musa</au><au>Shilovskiy, Igor</au><au>Valenta, Rudolf</au><au>Weber, Milena</au><au>Korneev, Artem</au><au>Tulaeva, Inna</au><au>Gattinger, Pia</au><au>Hage, Marianne</au><au>Hofer, Gerhard</au><au>Konradsen, Jon R.</au><au>Keller, Walter</au><au>Akinfenwa, Oluwatoyin</au><au>Poroshina, Alina</au><au>Ilina, Nataliya</au><au>Fedenko, Elena</au><au>Elisyutina, Olga</au><au>Litovkina, Alla</au><au>Smolnikov, Evgenii</au><au>Nikonova, Aleksandra</au><au>Rybalkin, Sergei</au><au>Aldobaev, Vladimir</au><au>Smirnov, Valeriy</au><au>Shershakova, Nadezhda</au><au>Petukhova, Olga</au><au>Kudlay, Dmitriy</au><au>Shatilov, Artem</au><au>Timofeeva, Anastasiya</au><au>Campana, Raffaela</au><au>Udin, Sergei</au><au>Skvortsova, Veronica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant PreS‐fusion protein vaccine for birch pollen and apple allergy</atitle><jtitle>Allergy (Copenhagen)</jtitle><addtitle>Allergy</addtitle><date>2024-04</date><risdate>2024</risdate><volume>79</volume><issue>4</issue><spage>1001</spage><epage>1017</epage><pages>1001-1017</pages><issn>0105-4538</issn><issn>1398-9995</issn><eissn>1398-9995</eissn><abstract>Background
IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome.
Methods
We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA.
Results
IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV.
Conclusion
The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
We designed a vaccine consisting of peptides derived from IgE epitopes of birch and apple allergens fused with HBV‐derived PreS. Aluminum hydroxide‐adsorbed AB‐PreS induces IgG antibodies specific for Bet v 1, Mal d 1, and HBV. IgG antibodies induced by AB‐PreS inhibit IgE binding of allergic patients IgE to Bet v 1 and Mal d 1 better than extract‐based vaccines. Anti‐PreS IgG may protect against HBV infection.Abbreviations: Ab‐PreS, recombinant protein, consisting of non‐allergenic peptides derived from the IgE binding sites of Bet v 1 and Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier; Bet v 1, major birch pollen allergen; HBV, hepatitis B virus; Ig, immunoglobulin; Mal d 1, cross‐reactive apple allergen; OD, optical density.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>37855043</pmid><doi>10.1111/all.15919</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-6126-4075</orcidid><orcidid>https://orcid.org/0000-0002-4609-2591</orcidid><orcidid>https://orcid.org/0000-0001-9610-0935</orcidid><orcidid>https://orcid.org/0000-0003-3091-1596</orcidid><orcidid>https://orcid.org/0000-0002-2261-958X</orcidid><orcidid>https://orcid.org/0000-0002-8232-6682</orcidid><orcidid>https://orcid.org/0000-0001-5944-3365</orcidid><orcidid>https://orcid.org/0000-0001-6724-8543</orcidid><orcidid>https://orcid.org/0000-0001-6444-6499</orcidid><orcidid>https://orcid.org/0000-0001-5343-4230</orcidid><orcidid>https://orcid.org/0000-0002-4675-8074</orcidid><orcidid>https://orcid.org/0000-0001-9309-9908</orcidid><orcidid>https://orcid.org/0000-0002-0400-2201</orcidid><orcidid>https://orcid.org/0000-0002-2494-3033</orcidid><orcidid>https://orcid.org/0000-0002-3556-969X</orcidid><orcidid>https://orcid.org/0000-0002-5021-9276</orcidid><orcidid>https://orcid.org/0000-0003-2815-280X</orcidid><orcidid>https://orcid.org/0000-0003-1878-4467</orcidid><orcidid>https://orcid.org/0000-0001-7745-8624</orcidid><orcidid>https://orcid.org/0000-0003-1302-4178</orcidid><orcidid>https://orcid.org/0000-0002-2107-1364</orcidid><orcidid>https://orcid.org/0000-0002-9248-6989</orcidid><orcidid>https://orcid.org/0000-0002-0911-8860</orcidid><orcidid>https://orcid.org/0000-0002-5825-2687</orcidid><orcidid>https://orcid.org/0000-0002-3339-2608</orcidid><orcidid>https://orcid.org/0000-0003-3780-2878</orcidid><orcidid>https://orcid.org/0000-0003-1864-8684</orcidid><orcidid>https://orcid.org/0000-0003-4961-9640</orcidid><orcidid>https://orcid.org/0000-0003-3358-5087</orcidid><orcidid>https://orcid.org/0000-0002-7817-8197</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0105-4538 |
| ispartof | Allergy (Copenhagen), 2024-04, Vol.79 (4), p.1001-1017 |
| issn | 0105-4538 1398-9995 1398-9995 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_825770 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | allergen allergen-specific immunotherapy Allergens Animals Antibodies Antigens, Plant Bet v 1 antigen Betula birch pollen-associated food allergy syndrome Blocking antibodies Cell activation Enzyme-linked immunosorbent assay Escherichia coli Food allergies Food Hypersensitivity - prevention & control Fusion protein Humans Immunization Immunoglobulin E Immunoglobulin G Immunotherapy Inflammation Leukocytes (basophilic) Mal d 1 antigen Malus molecular allergy vaccine Plant Proteins Pollen Proteins Rabbits Recombinant Fusion Proteins Vaccines Vaccines, Synthetic |
| title | Recombinant PreS‐fusion protein vaccine for birch pollen and apple allergy |
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