A phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18-59 years: An interim analysis in Indonesia

Eddy Fadlyana, Kusnandi Rusmil, Rodman Tarigan, Andri Reza Rahmadi, Susantina Prodjosoewojo, Yulia Sofiatin, Citra V Khrisna, Rini Mulia Sari, Lilis Setyaningsih, Fikrianti Surachman, Novilia Sjafri Bachtiar, Hadyana Sukandar, Imam Megantara, Chrysanti Murad, Krisna Nur A Pangesti, Vivi Setiawaty, Sunarjati Sudigdoadi, Yaling Hu, Qiang Gao, Cissy B Kartasasmita, Eddy Fadlyana, Kusnandi Rusmil, Rodman Tarigan, Andri Reza Rahmadi, Susantina Prodjosoewojo, Yulia Sofiatin, Citra V Khrisna, Rini Mulia Sari, Lilis Setyaningsih, Fikrianti Surachman, Novilia Sjafri Bachtiar, Hadyana Sukandar, Imam Megantara, Chrysanti Murad, Krisna Nur A Pangesti, Vivi Setiawaty, Sunarjati Sudigdoadi, Yaling Hu, Qiang Gao, Cissy B Kartasasmita

Abstract

Background: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine.

Methods: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose.

Results: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%.

Conclusions: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.

Keywords: Adults; Efficacy; Immunogenicity; SARS-CoV-2 Inactivated Vaccine; Safety.

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Participant Disposition.
Fig. 2
Fig. 2
Adverse Events occurring after the First and Second Vaccine Injection.

References

    1. Ophinni Y., Hasibuan A.S., Widhani A., Maria S., Koesnoe S., Yunihastuti E., et al. COVID-19 Vaccines: Current Status and Implication for Use in Indonesia. Acta Med Indones. 2020;52:388–412.
    1. WHO Coronavirus disease (COVID-19) Situation Report-132. 2020
    1. Gupta S.D. Coronavirus Pandemic: A Serious Threat to Humanity. J Health Manag. 2020;22(1):1–2. doi: 10.1177/0972063420921260.
    1. Zhu N.a., Zhang D., Wang W., Li X., Yang B.o., Song J., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–733. doi: 10.1056/NEJMoa2001017.
    1. García-Basteiro A.L., Chaccour C., Guinovart C., Llupià A., Brew J., Trilla A., et al. Monitoring the COVID-19 epidemic in the context of widespread local transmission. Lancet Respir Med. 2020;8(5):440–442. doi: 10.1016/S2213-2600(20)30162-4.
    1. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020 n.d. (accessed January 23, 2021).
    1. World Health Organization Weekly Epidemiological Update on COVID-19. World Heal Organ. 2020;1:4.
    1. WHO. Situation Report-7 INDONESIA Situation Report 19 Internal for SEARO. 2020.
    1. Wenjiang Fu1 2*, Jieni Li3 and Paul Scheet 4. Covid-19 Vaccine Efficacy: Accuracy, Uncertainty and Projection of Cases. MedRxiv 2020. 10.1101/2020.12.16.20248359.
    1. Lurie N., Saville M., Hatchett R., Halton J. Developing Covid-19 Vaccines at Pandemic Speed. N Engl J Med. 2020;382(21):1969–1973. doi: 10.1056/NEJMp2005630.
    1. WHO. WHO R&D Blueprint novel Coronavirus Outline of designs for experimental vaccines and therapeutics. vol. 205. 2020.
    1. Wang H., Zhang Y., Huang B., Deng W., Quan Y., Wang W., et al. Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell. 2020;182(3):713–721.e9. doi: 10.1016/j.cell.2020.06.008.
    1. Vellozzi C., Burwen D.R., Dobardzic A., Ball R., Walton K., Haber P. Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring. Vaccine. 2009;27(15):2114–2120. doi: 10.1016/j.vaccine.2009.01.125.
    1. Murdin A.D., Barreto L., Plotkin S. Inactivated poliovirus vaccine: Past and present experience. Vaccine. 1996;14(8):735–746. doi: 10.1016/0264-410X(95)00211-I.
    1. (WHO) WHO. Draft landscape and tracker of COVID-19 candidate vaccines 2021. (accessed January 25, 2021).
    1. Gao Q., Bao L., Mao H., Wang L., Xu K., Yang M., et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science (80-) 2020;369(6499):77–81. doi: 10.1126/science:abc1932.
    1. Zhang Y., Zeng G., Pan H., Li C., Hu Y., Chu K., et al. Articles Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years. Lancet Infect Dis. 2020
    1. KEMENKES. Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MenKes/413/2020 Tentang Pedoman Pencegahan dan Pengendalian Corona Virus Disease 2019 (Covid-19). MenKes/413/2020 2020;2019:207.
    1. Okba N.M.A., Müller M.A., Li W., Wang C., GeurtsvanKessel C.H., Corman V.M., et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg Infect Dis. 2020;26(7):1478–1488. doi: 10.3201/eid2607.200841.
    1. Jiang S., Hillyer C., Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol. 2020;41(5):355–359. doi: 10.1016/j.it.2020.03.007.
    1. Grzelak L., Temmam S., Planchais C., Demeret C., Huon C., Guivel-Benhassine F., et al. SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors. MedRxiv. 2020;17:25. doi: 10.1101/2020.04.21.20068858.
    1. SAGE (Strategic Advisory Group of Experts). Background document on the inactivated vaccine Sinovac-CoronaVac against COVID-19. 2021.
    1. Tanriover MD, Doğanay HL, Akova M, Güner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet 2021;398:213–22. 10.1016/S0140-6736(21)01429-X.
    1. Jara A., Undurraga E.A., González C., Paredes F., Fontecilla T., Jara G., et al. Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile. N Engl J Med. 2021;385(10):875–884. doi: 10.1056/NEJMoa2107715.
    1. Sinovac Announces Phase III Results of Its COVID-19 Vaccine-SINOVAC - Supply Vaccines to Eliminate Human Diseases n.d. (accessed March 17, 2021).
    1. CDC. Principles of Epidemiology | Lesson 3 - Section 6 n.d. (accessed February 22, 2021).
    1. Fda, Cber. Contains Nonbinding Recommendations Development and Licensure of Vaccines to Prevent COVID-19 Guidance for Industry. 2020.
    1. Fda, Cber. Contains Nonbinding Recommendations Emergency Use Authorization for Vaccines to Prevent COVID-19 Guidance for Industry Preface Public Comment. 2020.
    1. Folegatti P.M., Ewer K.J., Aley P.K., Angus B., Becker S., Belij-Rammerstorfer S., et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396:467–478. doi: 10.1016/S0140-6736(20)31604-4.
    1. Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine _ Enhanced Reader.pdf. N Engl J Med. 2020;383(27):2603–2615.
    1. (WHO) WHO. CONSIDERATIONS FOR EVALUATION OF COVID19 VACCINES 2020;21:1–14. (accessed January 25, 2021).

Source: PubMed

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