Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability
For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were develo...
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| Format: | Article |
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Elsevier
2023-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023018777 |
| _version_ | 1797851728168615936 |
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| author | Eduardo Federico Mufarrege Lucía Carolina Peña Marina Etcheverrigaray Anne S. De Groot William Martin |
| author_facet | Eduardo Federico Mufarrege Lucía Carolina Peña Marina Etcheverrigaray Anne S. De Groot William Martin |
| author_sort | Eduardo Federico Mufarrege |
| collection | DOAJ |
| description | For decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3).Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases. |
| first_indexed | 2024-04-09T19:22:32Z |
| format | Article |
| id | doaj.art-9ec60d2ab57e47fd9ae00c3c82af6b1f |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T19:22:32Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-9ec60d2ab57e47fd9ae00c3c82af6b1f2023-04-05T08:27:59ZengElsevierHeliyon2405-84402023-03-0193e14670Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stabilityEduardo Federico Mufarrege0Lucía Carolina Peña1Marina Etcheverrigaray2Anne S. De Groot3William Martin4UNL, CONICET, FBCB (School of Biochemistry and Biological Sciences), CBL (Biotechnological Center of Litoral), Ciudad Universitaria, Ruta Nacional 168, Km 472.4, C.C. 242, S3000ZAA, Santa Fe, Argentina; Corresponding author. Ciudad Universitaria, Paraje “El Pozo” – c.c 242, S3000ZAA, Santa Fe, Argentina.UNL, CONICET, FBCB (School of Biochemistry and Biological Sciences), CBL (Biotechnological Center of Litoral), Ciudad Universitaria, Ruta Nacional 168, Km 472.4, C.C. 242, S3000ZAA, Santa Fe, ArgentinaUNL, CONICET, FBCB (School of Biochemistry and Biological Sciences), CBL (Biotechnological Center of Litoral), Ciudad Universitaria, Ruta Nacional 168, Km 472.4, C.C. 242, S3000ZAA, Santa Fe, ArgentinaEpiVax, Inc., Providence, RI, 02903, USA; Institute for Immunology and Informatics, University of Rhode Island, Providence, RI, 02903, USAEpiVax, Inc., Providence, RI, 02903, USAFor decades, recombinant human interferon alpha (rhIFN-α2b) has been used to treat emerging and chronic viral diseases. However, rhIFN-α2b is immunogenic and has a short in vivo half-life. To solve these limitations, two long-lasting hyperglycosylated proteins with reduced immunogenicity were developed and designated as 4N-IFN(VAR1) and 4N-IFN(VAR3).Here, we continue to study the relevant characteristics of these therapeutic candidates. Thus, we demonstrated that both de-immunized IFN versions elicited significantly lower neutralizing antibody responses than the original molecule in HLA-DR1 transgenic mice, confirming our previous in vitro protein immunogenicity data. Also, we found that these biobetters exhibited remarkable stability when exposed to different physical factors that the protein product may encounter during its production process and storage, such as low pH, thermal stress, and repeated freezing/thawing cycles. Taking into consideration our previous and present results, 4N-IFN(VAR1) and 4N-IFN-4N(VAR3) appear to be valuable candidates for the treatment of human viral diseases.http://www.sciencedirect.com/science/article/pii/S2405844023018777IFN alphaImmunogenicityDe-immunizationEpiMatrixIn vivo assaysAnti-viral therapy |
| spellingShingle | Eduardo Federico Mufarrege Lucía Carolina Peña Marina Etcheverrigaray Anne S. De Groot William Martin Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability Heliyon IFN alpha Immunogenicity De-immunization EpiMatrix In vivo assays Anti-viral therapy |
| title | Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| title_full | Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| title_fullStr | Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| title_full_unstemmed | Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| title_short | Specific sequence mutations in a long-lasting rhIFN-α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| title_sort | specific sequence mutations in a long lasting rhifn α2b version reduce in vitro and in vivo immunogenicity and increase in vitro protein stability |
| topic | IFN alpha Immunogenicity De-immunization EpiMatrix In vivo assays Anti-viral therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023018777 |
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