A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2
Continued mutation of the SARS-CoV-2 genome has led to multiple waves of COVID-19 infections, and new variants have continued to emerge and dominate. The emergence of Omicron and its subvariants has substantially increased the infectivity of SARS-CoV-2. RBD genes of the wild-type SARS-CoV-2 strain a...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/11/10/1539 |
| _version_ | 1827719753682124800 |
|---|---|
| author | Tiantian Wang Jing Zheng Huifang Xu Zhongyi Wang Peng Sun Xuchen Hou Xin Gong Bin Zhang Jun Wu Bo Liu |
| author_facet | Tiantian Wang Jing Zheng Huifang Xu Zhongyi Wang Peng Sun Xuchen Hou Xin Gong Bin Zhang Jun Wu Bo Liu |
| author_sort | Tiantian Wang |
| collection | DOAJ |
| description | Continued mutation of the SARS-CoV-2 genome has led to multiple waves of COVID-19 infections, and new variants have continued to emerge and dominate. The emergence of Omicron and its subvariants has substantially increased the infectivity of SARS-CoV-2. RBD genes of the wild-type SARS-CoV-2 strain and the Delta, Omicron BA.1 and Omicron BA.2 variants were used to construct plasmids and express the proteins in glycoengineered <i>Pichia pastoris</i>. A stable 4 L-scale yeast fermentation and purification process was established to obtain high-purity RBD proteins with a complex glycoform N-glycosyl structure that was fucose-free. The RBD glycoproteins were combined with two adjuvants, Al(OH)<sub>3</sub> and CpG, which mitigated the typical disadvantage of low immunogenicity associated with recombinant subunit vaccines. To improve the broad-spectrum antiviral activity of the candidate vaccine, Delta RBD proteins were mixed with BA.2 RBD proteins at a ratio of 1:1 and then combined with two adjuvants—Al(OH)<sub>3</sub> and CpG—to prepare a bivalent vaccine. The bivalent vaccine effectively induced mice to produce pseudovirus-neutralizing antibodies against SARS-CoV-2 variants, Delta, Beta, and Omicron sublineages BA.1, BA.2, BA.5. The bivalent vaccine could neutralize the authentic wild-type SARS-CoV-2 strain, Delta, BA.1.1, BA.2.2, BA2.3, and BA.2.12.1 viruses, providing a new approach for improving population immunity and delivering broad-spectrum protection under the current epidemic conditions. |
| first_indexed | 2024-03-10T20:50:25Z |
| format | Article |
| id | doaj.art-fda0e636901f44209ceb62359128c9bd |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T20:50:25Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-fda0e636901f44209ceb62359128c9bd2023-11-19T18:24:12ZengMDPI AGVaccines2076-393X2023-09-011110153910.3390/vaccines11101539A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2Tiantian Wang0Jing Zheng1Huifang Xu2Zhongyi Wang3Peng Sun4Xuchen Hou5Xin Gong6Bin Zhang7Jun Wu8Bo Liu9Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaXiamen Center for Disease Control and Prevention, Xiamen 361000, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaDepartment of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, ChinaContinued mutation of the SARS-CoV-2 genome has led to multiple waves of COVID-19 infections, and new variants have continued to emerge and dominate. The emergence of Omicron and its subvariants has substantially increased the infectivity of SARS-CoV-2. RBD genes of the wild-type SARS-CoV-2 strain and the Delta, Omicron BA.1 and Omicron BA.2 variants were used to construct plasmids and express the proteins in glycoengineered <i>Pichia pastoris</i>. A stable 4 L-scale yeast fermentation and purification process was established to obtain high-purity RBD proteins with a complex glycoform N-glycosyl structure that was fucose-free. The RBD glycoproteins were combined with two adjuvants, Al(OH)<sub>3</sub> and CpG, which mitigated the typical disadvantage of low immunogenicity associated with recombinant subunit vaccines. To improve the broad-spectrum antiviral activity of the candidate vaccine, Delta RBD proteins were mixed with BA.2 RBD proteins at a ratio of 1:1 and then combined with two adjuvants—Al(OH)<sub>3</sub> and CpG—to prepare a bivalent vaccine. The bivalent vaccine effectively induced mice to produce pseudovirus-neutralizing antibodies against SARS-CoV-2 variants, Delta, Beta, and Omicron sublineages BA.1, BA.2, BA.5. The bivalent vaccine could neutralize the authentic wild-type SARS-CoV-2 strain, Delta, BA.1.1, BA.2.2, BA2.3, and BA.2.12.1 viruses, providing a new approach for improving population immunity and delivering broad-spectrum protection under the current epidemic conditions.https://www.mdpi.com/2076-393X/11/10/1539SARS-CoV-2RBDsubunit vaccinebivalent vaccineglycoengineered yeast |
| spellingShingle | Tiantian Wang Jing Zheng Huifang Xu Zhongyi Wang Peng Sun Xuchen Hou Xin Gong Bin Zhang Jun Wu Bo Liu A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 Vaccines SARS-CoV-2 RBD subunit vaccine bivalent vaccine glycoengineered yeast |
| title | A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 |
| title_full | A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 |
| title_fullStr | A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 |
| title_full_unstemmed | A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 |
| title_short | A Delta–Omicron Bivalent Subunit Vaccine Elicited Antibody Responses in Mice against Both Ancestral and Variant Strains of SARS-CoV-2 |
| title_sort | delta omicron bivalent subunit vaccine elicited antibody responses in mice against both ancestral and variant strains of sars cov 2 |
| topic | SARS-CoV-2 RBD subunit vaccine bivalent vaccine glycoengineered yeast |
| url | https://www.mdpi.com/2076-393X/11/10/1539 |
| work_keys_str_mv | AT tiantianwang adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT jingzheng adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT huifangxu adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT zhongyiwang adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT pengsun adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT xuchenhou adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT xingong adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT binzhang adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT junwu adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT boliu adeltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT tiantianwang deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT jingzheng deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT huifangxu deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT zhongyiwang deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT pengsun deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT xuchenhou deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT xingong deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT binzhang deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT junwu deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 AT boliu deltaomicronbivalentsubunitvaccineelicitedantibodyresponsesinmiceagainstbothancestralandvariantstrainsofsarscov2 |