Clinical and Experimental Vaccine Research

  • 제13권4호
  • /
  • Pages.329-337
  • /
  • 2024
  • /
  • 2287-3651(pISSN)
  • /
  • 2287-366X(eISSN)
대한백신학회 (The Korean Vaccine Society)
권호 표지
DOI QR코드

DOI QR Code

Safety and immunogenicity of PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine as a booster against SARS-CoV-2: a phase II, open-label, randomized, double-blinded study

  • 투고 : 2024.06.20
  • 심사 : 2024.09.21
  • 발행 : 2024.10.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: This study evaluated the safety and immunogenicity of the PIKA-adjuvanted recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein subunit vaccine as a booster dose for healthy adults who had previously received two or more doses of an inactivated coronavirus disease 2019 (COVID-19) vaccine. Materials and Methods: The study was a phase II multicenter, double-blinded, comparatorcontrolled, randomized trial. Participants were randomly assigned to receive either the PIKA COVID-19 vaccine booster dose or an inactivated COVID-19 vaccine (Sinovac, China). Safety was assessed based on adverse events, while immunogenicity was measured by neutralizing antibodies against SARS-CoV-2 and serum immunoglobulin G (IgG) levels. Data on safety and immunogenicity were collected in the short-term (within 14 days after the booster dose) and long-term (from 90 to 365 days after the booster dose). Results: The PIKA-adjuvanted vaccine demonstrated a significant increase in neutralizing antibodies against the Omicron variant (geometric mean ratio [GMR]=2.0 on day 7, p-value <0.001; GMR=2.7 on day 14, p-value <0.001) and the wild type SARS-CoV-2 virus (GMR=2.3 on day 7, p-value <0.001; GMR=2.8 on day 14, p-value<0.001) in the early post-vaccination period when compared to the inactivated vaccine. Additionally, the PIKA COVID-19 vaccine showed higher seroconversion rates for neutralizing antibodies against both variants during the first 14 days post-vaccination. However, there were no significant differences in neutralizing antibody levels between the two vaccines from day 90 to day 360 post-vaccination. Serum IgG antibody levels for the PIKA COVID-19 vaccine were also higher throughout the study period. The incidence of adverse events was slightly higher in the PIKA COVID-19 group, with the most common events being pain at the injection site and headache. All adverse events were mild or moderate, with no reports of severe or life-threatening adverse events in either group. Conclusion: The PIKA COVID-19 vaccine, when administered as a booster dose, showed promising short- and long-term immunogenicity with no emergent safety issues identified. The booster dose of the PIKA COVID-19 vaccine elicited a robust immune response against various SARS-CoV-2 variants and provided some seroprotection for up to 360 days (ClinicalTrials. gov registration number: NCT05463419).

키워드

과제정보

We extend our special thanks to all the participants, investigators, and the dedicated study site staff for their invaluable support throughout the research. We also express our appreciation to Sinovac Biotech for providing the comparator and to Novotech Health Holdings for their assistance with clinical trial operations. This work was funded and supported by YS Biopharma Co. Ltd.

참고문헌

  1. Ganesh B, Rajakumar T, Malathi M, et al. Epidemiology and pathobiology of SARS-CoV-2 (COVID-19) in comparison with SARS, MERS: an updated overview of current knowledge and future perspectives. Clin Epidemiol Glob Health 2021;10:100694.
  2. World Health Organization. WHO COVID-19 Dashboard. Geneva: World Health Organization; 2020.
  3. World Health Organization. COVID-19 advice for the public: getting vaccinated. Geneva: World Health Organization; 2023.
  4. Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms. Comput Struct Biotechnol J 2021;19:2508-17.
  5. Lau YF, Tang LH, McCall AW, Ooi EE, Subbarao K. An adjuvant for the induction of potent, protective humoral responses to an H5N1 influenza virus vaccine with antigen-sparing effect in mice. J Virol 2010;84:8639-49.
  6. Lau YF, Tang LH, Ooi EE, Subbarao K. Activation of the innate immune system provides broad-spectrum protection against influenza A viruses with pandemic potential in mice. Virology 2010;406:80-7.
  7. Shen E, Li L, Li L, et al. PIKA as an adjuvant enhances specific humoral and cellular immune responses following the vaccination of mice with HBsAg plus PIKA. Cell Mol Immunol 2007;4:113-20.
  8. Bezbaruah R, Borah P, Kakoti BB, et al. Developmental landscape of potential vaccine candidates based on viral vector for prophylaxis of COVID-19. Front Mol Biosci 2021;8:635337.
  9. Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020;41:1141-9.
  10. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281-92.
  11. Gai WW, Zhang Y, Zhou DH, Chen YQ, Yang JY, Yan HM. PIKA provides an adjuvant effect to induce strong mucosal and systemic humoral immunity against SARS-CoV. Virol Sin 2011;26:81-94.
  12. Liu Y, Tan LH, Zhang N, Zhang Y, Mojares ZR. Safety, tolerability, and immunogenicity of PIKA-adjuvanted recombinant SARS-CoV-2 spike (S) protein subunit vaccine in healthy adults: interim results of an open-label and randomised phase 1 clinical trial. medRxiv [Preprint] 2022 Nov 22. https://doi.org/10.1101/2022.11.20.22282565
  13. Chakraborty C, Sharma AR, Bhattacharya M, Lee SS. A detailed overview of immune escape, antibody escape, partial vaccine escape of SARS-CoV-2 and their emerging variants with escape mutations. Front Immunol 2022;13:801522.
  14. Chatterjee S, Bhattacharya M, Nag S, Dhama K, Chakraborty C. A detailed overview of SARS-CoV-2 Omicron: its sub-variants, mutations and pathophysiology, clinical characteristics, immunological landscape, immune escape, and therapies. Viruses 2023;15:167.
  15. Chi WY, Li YD, Huang HC, et al. COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection. J Biomed Sci 2022;29:82.
  16. Ghildiyal T, Rai N, Mishra Rawat J, et al. Challenges in emerging vaccines and future promising candidates against SARS-CoV-2 variants. J Immunol Res 2024;2024:9125398.
  17. Wang Z, An J, Liu K, et al. A potent, broadly protective vaccine against SARS-CoV-2 variants of concern. NPJ Vaccines 2022;7:144.
  18. Zhao F, Zai X, Zhang Z, Xu J, Chen W. Challenges and developments in universal vaccine design against SARS-CoV-2 variants. NPJ Vaccines 2022;7:167.
  19. Larsen MD, de Graaf EL, Sonneveld ME, et al. Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity. Science 2021;371:eabc8378.
  20. Pongracz T, Nouta J, Wang W, et al. Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19. EBioMedicine 2022;78:103957.
  21. Siekman SL, Pongracz T, Wang W, et al. The IgG glycome of SARS-CoV-2 infected individuals reflects disease course and severity. Front Immunol 2022;13:993354.
  22. Asyura MM, Chandra AP, Agussalim A, Soloan G. Immunogenicity and safety analysis of inactivated virus vaccine against SARS-CoV-2: a systematic review of phase 1/2 clinical trials. J Asian Med Stud Assoc 2021;9:169-84.
  23. Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021;21:803-12.
  24. Zhang Y, Zeng G, Pan H, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis 2021;21:181-92.
  25. Hattab D, Amer MF, Al-Alami ZM, Bakhtiar A. SARS-CoV-2 journey: from Alpha variant to Omicron and its sub-variants. Infection 2024;52:767-86.