Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial
Summary: Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity i...
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Elsevier
2022-09-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537022002991 |
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| author | Joon Young Song Won Suk Choi Jung Yeon Heo Jin Soo Lee Dong Sik Jung Shin-Woo Kim Kyung-Hwa Park Joong Sik Eom Su Jin Jeong Jacob Lee Ki Tae Kwon Hee Jung Choi Jang Wook Sohn Young Keun Kim Ji Yun Noh Woo Joo Kim François Roman Maria Angeles Ceregido Francesca Solmi Agathe Philippot Alexandra C. Walls Lauren Carter David Veesler Neil P. King Hun Kim Ji Hwa Ryu Su Jeen Lee Yong Wook Park Ho Keun Park Hee Jin Cheong |
| author_facet | Joon Young Song Won Suk Choi Jung Yeon Heo Jin Soo Lee Dong Sik Jung Shin-Woo Kim Kyung-Hwa Park Joong Sik Eom Su Jin Jeong Jacob Lee Ki Tae Kwon Hee Jung Choi Jang Wook Sohn Young Keun Kim Ji Yun Noh Woo Joo Kim François Roman Maria Angeles Ceregido Francesca Solmi Agathe Philippot Alexandra C. Walls Lauren Carter David Veesler Neil P. King Hun Kim Ji Hwa Ryu Su Jeen Lee Yong Wook Park Ho Keun Park Hee Jin Cheong |
| author_sort | Joon Young Song |
| collection | DOAJ |
| description | Summary: Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19–55 years; stage II, 240 healthy adults aged 19–85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study. |
| first_indexed | 2024-12-10T09:42:15Z |
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| id | doaj.art-80ddadf93d8141ebb97f5b2dfc32f0bc |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-12-10T09:42:15Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-80ddadf93d8141ebb97f5b2dfc32f0bc2022-12-22T01:53:58ZengElsevierEClinicalMedicine2589-53702022-09-0151101569Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trialJoon Young Song0Won Suk Choi1Jung Yeon Heo2Jin Soo Lee3Dong Sik Jung4Shin-Woo Kim5Kyung-Hwa Park6Joong Sik Eom7Su Jin Jeong8Jacob Lee9Ki Tae Kwon10Hee Jung Choi11Jang Wook Sohn12Young Keun Kim13Ji Yun Noh14Woo Joo Kim15François Roman16Maria Angeles Ceregido17Francesca Solmi18Agathe Philippot19Alexandra C. Walls20Lauren Carter21David Veesler22Neil P. King23Hun Kim24Ji Hwa Ryu25Su Jeen Lee26Yong Wook Park27Ho Keun Park28Hee Jin Cheong29Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of KoreaDepartment of Infectious Diseases, Ajou University School of Medicine, Suwon, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Inha University College of Medicine, Incheon, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Centre, Gachon University College of Medicine, Incheon, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Seoul, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Yonsei University Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of KoreaGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Wavre, BelgiumDepartment of Biochemistry, University of Washington, WA, USA; Howard Hughes Medical Institute, University of Washington, WA, USADepartment of Biochemistry, University of Washington, WA, USA; Institute for Protein Design, University of Washington, WA, USADepartment of Biochemistry, University of Washington, WA, USA; Howard Hughes Medical Institute, University of Washington, WA, USADepartment of Biochemistry, University of Washington, WA, USA; Institute for Protein Design, University of Washington, WA, USADepartment of R&D, SK Bioscience, Seongnam, Republic of KoreaDepartment of R&D, SK Bioscience, Seongnam, Republic of KoreaDepartment of R&D, SK Bioscience, Seongnam, Republic of KoreaDepartment of R&D, SK Bioscience, Seongnam, Republic of KoreaDepartment of R&D, SK Bioscience, Seongnam, Republic of KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; Corresponding author at: Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Gurodong-ro 148, Guro-gu, Seoul 08308, Republic of Korea.Summary: Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19–55 years; stage II, 240 healthy adults aged 19–85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.http://www.sciencedirect.com/science/article/pii/S2589537022002991SARS-CoV-2COVID-19Recombinant protein vaccineNanoparticle vaccineHumoral immunityCellular immunity |
| spellingShingle | Joon Young Song Won Suk Choi Jung Yeon Heo Jin Soo Lee Dong Sik Jung Shin-Woo Kim Kyung-Hwa Park Joong Sik Eom Su Jin Jeong Jacob Lee Ki Tae Kwon Hee Jung Choi Jang Wook Sohn Young Keun Kim Ji Yun Noh Woo Joo Kim François Roman Maria Angeles Ceregido Francesca Solmi Agathe Philippot Alexandra C. Walls Lauren Carter David Veesler Neil P. King Hun Kim Ji Hwa Ryu Su Jeen Lee Yong Wook Park Ho Keun Park Hee Jin Cheong Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial EClinicalMedicine SARS-CoV-2 COVID-19 Recombinant protein vaccine Nanoparticle vaccine Humoral immunity Cellular immunity |
| title | Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial |
| title_full | Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial |
| title_fullStr | Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial |
| title_full_unstemmed | Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial |
| title_short | Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial |
| title_sort | safety and immunogenicity of a sars cov 2 recombinant protein nanoparticle vaccine gbp510 adjuvanted with as03 a randomised placebo controlled observer blinded phase 1 2 trial |
| topic | SARS-CoV-2 COVID-19 Recombinant protein vaccine Nanoparticle vaccine Humoral immunity Cellular immunity |
| url | http://www.sciencedirect.com/science/article/pii/S2589537022002991 |
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