Safety and immunogenicity of MVC-COV1901 vaccine in older adults: Phase 2 randomized dose-comparison trial

Alexander Waits, Jau-Yuan Chen, Wei-Hong Cheng, Jih-I Yeh, Szu-Min Hsieh, Charles Chen, Robert Janssen, Chia En Lien, Tzou-Yien Lin, Alexander Waits, Jau-Yuan Chen, Wei-Hong Cheng, Jih-I Yeh, Szu-Min Hsieh, Charles Chen, Robert Janssen, Chia En Lien, Tzou-Yien Lin

Abstract

Introduction: Older adults are subject to higher COVID-19 infection and mortality rates. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine have been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age, however, older adults were under-represented.

Methods: A double-blind, randomized, multi-center study compared safety and immunogenicity of high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart in 420 participants of 65 years and older. The results have been stratified by the comorbidity status.

Results: Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities.

Conclusion: Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommend high dose for immunization of elder adults with MVC-COV1901. The clinical trial was registered at https://ichgcp.net/clinical-trials-registry/NCT04822025" title="See in ClinicalTrials.gov">NCT04822025).

Keywords: Immunogenicity; Immunosenescence; MVC-COV1901 vaccine; Older adults; SARS-Cov-2.

Conflict of interest statement

Declaration of Competing Interest Chen C and Lien CE are employees of Medigen Vaccine Biologics Corporation. Waits A received consultancy fee from Medigen Vaccine Biologics Corporation. Other authors report no conflict of interest.

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Study design.
Fig. 2
Fig. 2
Solicited local and systemic adverse events occurring within 7 days after first and second dose of MVC-COV1901 vaccine in mid- and high-dose groups in the safety set. (a) Safety set with all the participants (N=420). (b) Safety set with any comorbidities (n=149). (c) Safety set without any comorbidities (n=271). The comorbidities include cancer, chronic kidney disease, chronic obstruction pulmonary disease, heart conditions, obesity. Adverse events were graded as mild (grade 1), moderate (grade 2), or severe (grade 3).
Fig. 3
Fig. 3
Immunogenicity of high and mid dose MVC-COV1901 vaccine in 65-88 years old. (a) Neutralizing antibody titers (NT50) against SARS-CoV-2. (b) Binding antibody titers (IgG) against SARS-CoV-2. Error bars represent 95% confidence intervals of the geometric mean titers. Black dotted lines represent lower and upper limits of detection. Comorbidities include cancer, chronic kidney disease, chronic obstruction pulmonary disease, heart conditions, obesity. HD – high dose, 25mcg S-2P of MVC-COV1901 vaccine; MD – mid-dose, 15 mcg S-2P of MVC-COV1901 vaccine.

References

    1. Anderson E.J., Rouphael N.G., Widge A.T., Jackson L.A., Roberts P.C., Makhene M., et al. Safety and Immunogenicity of Sars-Cov-2 Mrna-1273 Vaccine in Older Adults. N Engl J Med. 2020;383:2427–2438.
    1. Centers for Disease Control and Prevention. Science Brief: Evidence Used to Update the List of Underlying Medical Conditions Associated with Higher Risk for Severe Covid-19, , Last Access: Apr 15, 2022.
    1. Formica N., Mallory R., Albert G., Robinson M., Plested J.S., Cho I., et al. Different Dose Regimens of a Sars-Cov-2 Recombinant Spike Protein Vaccine (Nvx-Cov2373) in Younger and Older Adults: A Phase 2 Randomized Placebo-Controlled Trial. PLoS Med. 2021;18
    1. Haas E.J., McLaughlin J.M., Khan F., Angulo F.J., Anis E., Lipsitch M., et al. Infections, Hospitalisations, and Deaths Averted Via a Nationwide Vaccination Campaign Using the Pfizer–Biontech Bnt162b2 Mrna Covid-19 Vaccine in Israel: A Retrospective Surveillance Study. Lancet Infect Dis. 2021
    1. Heath P.T., Galiza E.P., Baxter D.N., Boffito M., Browne D., Burns F., et al. Safety and Efficacy of Nvx-Cov2373 Covid-19 Vaccine. N Engl J Med. 2021;385:1172–1183.
    1. Hsieh S.-M., Liu M.-C., Chen Y.-H., Lee W.-S., Hwang S.-J., Cheng S.-H., et al. Lancet Respir Med; Taiwan: 2021. Safety and Immunogenicity of Cpg 1018 and Aluminium Hydroxide-Adjuvanted Sars-Cov-2 S-2p Protein Vaccine Mvc-Cov1901: Interim Results of a Large-Scale, Double-Blind, Randomised, Placebo-Controlled Phase 2 Trial.
    1. Hyer R.N., Janssen R.S. Immunogenicity and Safety of a 2-Dose Hepatitis B Vaccine, Hbsag/Cpg 1018, in Persons with Diabetes Mellitus Aged 60-70 Years. Vaccine. 2019;37:5854–5861.
    1. Janssen J.M., Heyward W.L., Martin J.T., Janssen R.S. Immunogenicity and Safety of an Investigational Hepatitis B Vaccine with a Toll-Like Receptor 9 Agonist Adjuvant (Hbsag-1018) Compared with a Licensed Hepatitis B Vaccine in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus. Vaccine. 2015;33:833–837.
    1. Jantzen R., Maltais M., Broët P. Socio-Demographic Factors Associated with Covid-19 Vaccine Hesitancy among Middle-Aged Adults During the Quebec's Vaccination Campaign. Front Public Health. 2022;10
    1. Khoury D.S., Cromer D., Reynaldi A., Schlub T.E., Wheatley A.K., Juno J.A., et al. Neutralizing Antibody Levels Are Highly Predictive of Immune Protection from Symptomatic Sars-Cov-2 Infection. Nat Med. 2021;27:1205–1211.
    1. Li J., Hui A., Zhang X., Yang Y., Tang R., Ye H., et al. Safety and Immunogenicity of the Sars-Cov-2 Bnt162b1 Mrna Vaccine in Younger and Older Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Study. Nat Med. 2021;27:1062–1070.
    1. Lien C.E., Lin Y.-J., Lin Y.-L., Tai I.-C., Chen C. medRxiv; 2021. The Age-Dependent Immunogenicity after Two Doses of Mvc-Cov1901 Vaccine. 2021.2012.2012.21267573.
    1. Masuda T., Murakami K., Sugiura K., Sakui S., Schuring R.P., Mori M. Safety and Immunogenicity of Nvx-Cov2373 (Tak-019) Vaccine in Healthy Japanese Adults: Interim Report of a Phase I/Ii Randomized Controlled Trial. Vaccine. 2022
    1. McElhaney J.E., Verschoor C.P., Andrew M.K., Haynes L., Kuchel G.A., Pawelec G. The Immune Response to Influenza in Older Humans: Beyond Immune Senescence. Immun Ageing. 2020;17:1–10.
    1. Naaber P., Tserel L., Kangro K., Sepp E., Jürjenson V., Adamson A., et al. Lancet Reg Health Eur; 2021. Dynamics of Antibody Response to Bnt162b2 Vaccine after Six Months: A Longitudinal Prospective Study.
    1. Our World in Data. Share of People Who Completed the Initial Covid-19 Vaccination Protocol by Age, , Last Access: Apr 14, 2022.
    1. Ramasamy M.N., Minassian A.M., Ewer K.J., Flaxman A.L., Folegatti P.M., Owens D.R., et al. Safety and Immunogenicity of Chadox1 Ncov-19 Vaccine Administered in a Prime-Boost Regimen in Young and Old Adults (Cov002): A Single-Blind, Randomised, Controlled, Phase 2/3 Trial. Lancet. 2020;396:1979–1993.
    1. Schenkelberg T. Vaccine-Induced Protection in Aging Adults and Pandemic Response. Biochem Biophys Res Commun. 2021;538:218.
    1. Siu J.Y.-m., Cao Y., Shum D.H.K. Perceptions of and Hesitancy toward Covid-19 Vaccination in Older Chinese Adults in Hong Kong: A Qualitative Study. BMC Geriatr. 2022;22:288.
    1. Soiza R.L., Scicluna C., Thomson E.C. Efficacy and Safety of Covid-19 Vaccines in Older People. Age Ageing. 2021;50:279–283.
    1. Taiwan Centers for Disease Control. Weekly Number of Suspected Covid-19 Cases Reported, , Last Access: Aug 22, 2022.
    1. Tan M., Straughan P.T., Cheong G. Information Trust and Covid-19 Vaccine Hesitancy Amongst Middle-Aged and Older Adults in Singapore: A Latent Class Analysis Approach. Soc Sci Med. 2022;296
    1. US Food and Drug Administration. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, , Last Access: Aug 22, 2022.
    1. Veronese N., Petrovic M., Benetos A., Denkinger M., Gudmundsson A., Knol W., et al. Underrepresentation of Older Adults in Clinical Trials on Covid-19 Vaccines: A Systematic Review. Ageing Res Rev. 2021;71
    1. World Health Organization. Who Coronavirus (Covid-19) Dashboard, , Last Access: Aug 22, 2022.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться