A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB
Waves of breakthrough infections by SARS-CoV-2 Omicron subvariants currently pose a global challenge to the control of the COVID-19 pandemic. We previously reported a pVAX1-based DNA vaccine candidate, pAD1002, that encodes a receptor-binding domain (RBD) chimera of SARS-CoV-1 and Omicron BA.1. In m...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/4/778 |
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| author | Yuan Ding Feng Fan Xin Xu Gan Zhao Xin Zhang Huiyun Zhao Limei Wang Bin Wang Xiao-Ming Gao |
| author_facet | Yuan Ding Feng Fan Xin Xu Gan Zhao Xin Zhang Huiyun Zhao Limei Wang Bin Wang Xiao-Ming Gao |
| author_sort | Yuan Ding |
| collection | DOAJ |
| description | Waves of breakthrough infections by SARS-CoV-2 Omicron subvariants currently pose a global challenge to the control of the COVID-19 pandemic. We previously reported a pVAX1-based DNA vaccine candidate, pAD1002, that encodes a receptor-binding domain (RBD) chimera of SARS-CoV-1 and Omicron BA.1. In mouse and rabbit models, pAD1002 plasmid induced cross-neutralizing Abs against heterologous sarbecoviruses, including SARS-CoV-1 and SARS-CoV-2 wildtype, Delta and Omicron variants. However, these antisera failed to block the recent emerging Omicron subvariants BF.7 and BQ.1. To solve this problem, we replaced the BA.1 RBD-encoding DNA sequence in pAD1002 with that of BA.4/5. The resulting construct, namely pAD1016, elicited SARS-CoV-1 and SARS-CoV-2 RBD-specific IFN-γ<sup>+</sup> cellular responses in BALB/c and C57BL/6 mice. More importantly, pAD1016 vaccination in mice, rabbits and pigs generated serum Abs capable of neutralizing pseudoviruses representing multiple SARS-CoV-2 Omicron subvariants including BA.2, BA.4/5, BF.7, BQ.1 and XBB. As a booster vaccine for inactivated SARS-CoV-2 virus preimmunization in mice, pAD1016 broadened the serum Ab neutralization spectrum to cover the Omicron BA.4/5, BF7 and BQ.1 subvariants. These preliminary data highlight the potential benefit of pAD1016 in eliciting neutralizing Abs against broad-spectrum Omicron subvariants in individuals previously vaccinated with inactivated prototype SARS-CoV-2 virus and suggests that pAD1016 is worthy of further translational study as a COVID-19 vaccine candidate. |
| first_indexed | 2024-03-11T04:27:26Z |
| format | Article |
| id | doaj.art-b336970260114a6d89d0fe7ac0ff0b3d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T04:27:26Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-b336970260114a6d89d0fe7ac0ff0b3d2023-11-17T21:41:37ZengMDPI AGVaccines2076-393X2023-03-0111477810.3390/vaccines11040778A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBBYuan Ding0Feng Fan1Xin Xu2Gan Zhao3Xin Zhang4Huiyun Zhao5Limei Wang6Bin Wang7Xiao-Ming Gao8Advaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaAdvaccine Biopharmaceutics (Suzhou) Co., Ltd., Suzhou 215123, ChinaWaves of breakthrough infections by SARS-CoV-2 Omicron subvariants currently pose a global challenge to the control of the COVID-19 pandemic. We previously reported a pVAX1-based DNA vaccine candidate, pAD1002, that encodes a receptor-binding domain (RBD) chimera of SARS-CoV-1 and Omicron BA.1. In mouse and rabbit models, pAD1002 plasmid induced cross-neutralizing Abs against heterologous sarbecoviruses, including SARS-CoV-1 and SARS-CoV-2 wildtype, Delta and Omicron variants. However, these antisera failed to block the recent emerging Omicron subvariants BF.7 and BQ.1. To solve this problem, we replaced the BA.1 RBD-encoding DNA sequence in pAD1002 with that of BA.4/5. The resulting construct, namely pAD1016, elicited SARS-CoV-1 and SARS-CoV-2 RBD-specific IFN-γ<sup>+</sup> cellular responses in BALB/c and C57BL/6 mice. More importantly, pAD1016 vaccination in mice, rabbits and pigs generated serum Abs capable of neutralizing pseudoviruses representing multiple SARS-CoV-2 Omicron subvariants including BA.2, BA.4/5, BF.7, BQ.1 and XBB. As a booster vaccine for inactivated SARS-CoV-2 virus preimmunization in mice, pAD1016 broadened the serum Ab neutralization spectrum to cover the Omicron BA.4/5, BF7 and BQ.1 subvariants. These preliminary data highlight the potential benefit of pAD1016 in eliciting neutralizing Abs against broad-spectrum Omicron subvariants in individuals previously vaccinated with inactivated prototype SARS-CoV-2 virus and suggests that pAD1016 is worthy of further translational study as a COVID-19 vaccine candidate.https://www.mdpi.com/2076-393X/11/4/778COVID-19SARS-CoV-2DNA vaccineRBD chimeraOmicron |
| spellingShingle | Yuan Ding Feng Fan Xin Xu Gan Zhao Xin Zhang Huiyun Zhao Limei Wang Bin Wang Xiao-Ming Gao A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB Vaccines COVID-19 SARS-CoV-2 DNA vaccine RBD chimera Omicron |
| title | A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB |
| title_full | A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB |
| title_fullStr | A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB |
| title_full_unstemmed | A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB |
| title_short | A COVID-19 DNA Vaccine Candidate Elicits Broadly Neutralizing Antibodies against Multiple SARS-CoV-2 Variants including the Currently Circulating Omicron BA.5, BF.7, BQ.1 and XBB |
| title_sort | covid 19 dna vaccine candidate elicits broadly neutralizing antibodies against multiple sars cov 2 variants including the currently circulating omicron ba 5 bf 7 bq 1 and xbb |
| topic | COVID-19 SARS-CoV-2 DNA vaccine RBD chimera Omicron |
| url | https://www.mdpi.com/2076-393X/11/4/778 |
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