Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine :  A Randomized Clinical Trial

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Key Points

Question

Do the protein-based SARS-CoV-2 vaccines (FINLAY-FR-2 and FINLAY-FR-1A) provide safe and effective protection against SARS-CoV-2?

Findings

In this randomized clinical trial including 23 959 individuals, vaccine efficacy for prevention of polymerase chain reaction (PCR)–positive symptomatic COVID-19 was 49.7%; severe disease, 76.8%; and hospitalization, 77.7% after the 2-dose regimen of FINLAY-FR-2, which improved to 64.9% for prevention of PCR-positive symptomatic COVID-19, 96.6% for prevention of severe disease, and 96.6% for prevention of hospitalization in recipients of a 2-dose regimen of FINLAY-FR-2 and a third dose of FINLAY-FR-1A. The incidence of serious adverse events was lower than 0.1%.

Meaning

The findings of this trial suggest that FINLAY-FR-2, in combination with a third dose of FINLAY-FR-1A, is a safe vaccine inducing a potent immune response against COVID-19.

Abstract

Importance

The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown.

Objective

To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults.

Design, Setting, and Participants

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021.

Interventions

In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection.

Main Outcomes and Measures

The primary outcome was polymerase chain reaction–confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed.

Results

In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths.

Conclusions and Relevance

In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19–related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price.

Trial Registration

isrctn.org Identifier: IRCT20210303050558N1

Abstract

This randomized clinical trial evaluates the efficacy and safety of the FINLAY-FR-2 and FINLAY-FR-1A COVID-19 vaccines in the Iranian population.

Related collections

Most cited references 32

Record: found
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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Lindsey Baden, Hana El Sahly, Brandon Essink … (2020)

Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)

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Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

Jamie Lopez Bernal, Nick Andrews, Charlotte Gower … (2021)

Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. Methods We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike ( S ) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status. Results Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)

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BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Noa Dagan, Noam Barda, Eldad Kepten … (2021)

Abstract Background As mass vaccination campaigns against coronavirus disease 2019 (Covid-19) commence worldwide, vaccine effectiveness needs to be assessed for a range of outcomes across diverse populations in a noncontrolled setting. In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Methods All persons who were newly vaccinated during the period from December 20, 2020, to February 1, 2021, were matched to unvaccinated controls in a 1:1 ratio according to demographic and clinical characteristics. Study outcomes included documented infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), symptomatic Covid-19, Covid-19–related hospitalization, severe illness, and death. We estimated vaccine effectiveness for each outcome as one minus the risk ratio, using the Kaplan–Meier estimator. Results Each study group included 596,618 persons. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% (95% confidence interval [CI], 40 to 51) and 92% (95% CI, 88 to 95); for symptomatic Covid-19, 57% (95% CI, 50 to 63) and 94% (95% CI, 87 to 98); for hospitalization, 74% (95% CI, 56 to 86) and 87% (95% CI, 55 to 100); and for severe disease, 62% (95% CI, 39 to 80) and 92% (95% CI, 75 to 100), respectively. Estimated effectiveness in preventing death from Covid-19 was 72% (95% CI, 19 to 100) for days 14 through 20 after the first dose. Estimated effectiveness in specific subpopulations assessed for documented infection and symptomatic Covid-19 was consistent across age groups, with potentially slightly lower effectiveness in persons with multiple coexisting conditions. Conclusions This study in a nationwide mass vaccination setting suggests that the BNT162b2 mRNA vaccine is effective for a wide range of Covid-19–related outcomes, a finding consistent with that of the randomized trial.

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Author and article information

Journal

Journal ID (nlm-ta): JAMA Netw Open

Journal ID (iso-abbrev): JAMA Netw Open

Title: JAMA Network Open

Publisher: American Medical Association

ISSN (Electronic): 2574-3805

Publication date (Electronic): 3 May 2023

Publication date Collection: May 2023

Publication date PMC-release: 3 May 2023

Volume: 6

Issue: 5

Electronic Location Identifier: e2310302

Affiliations

[1 ]Department of Epidemiology and Biostatistics, Research Centre for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran

[2 ]HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran

[3 ]School of Public Health, Brown University, Providence, Rhode Island

[4 ]Centre on Drug Policy Evaluation, St. Michael's Hospital, Toronto, Ontario, Canada

[5 ]The Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada

[6 ]Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran

[7 ]Department of Biostatistics and Epidemiology, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran

[8 ]COVID-19 National Reference Laboratory, Pasteur Institute of Iran, Tehran, Iran

[9 ]Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran

[10 ]Shiraz University of Medical Sciences, Shiraz, Iran

[11 ]Brucellosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

[12 ]Internal Medicine Department, Zanjan University of Medical Sciences, Zanjan, Iran

[13 ]Zanjan Metabolic Diseases Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

[14 ]Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

[15 ]Quality Control Department, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran

[16 ]Department of Genetics, School of Medicine, Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

[17 ]Pasteur Institute of Iran, Tehran, Iran

[18 ]Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran

[19 ]Department of Infectious Diseases, Antimicrobial Resistance Research Center, Mazandaran University of Medical Sciences, Sari, Iran

[20 ]Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

[21 ]Department of Infectious Diseases, Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

[22 ]Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran

[23 ]Cancer Control Research, BC Cancer Research Centre, Vancouver, British Columbia, Canada

[24 ]Shahid Sadoughi University of Medical Sciences, Yazd, Iran

[25 ]Pedro Kourí Tropical Medicine Institute, Havana, Cuba

[26 ]Cybernetics, Mathematics and Physics Institute, Havana, Cuba

[27 ]Finlay Vaccine Institute, Havana

[28 ]Centre for Communicable Disease Control, Ministry of Health and Medical Education, Tehran, Iran

[29 ]Department of Infectious Disease and Tropical Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

[30 ]Department of Infectious Disease, School of Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

[31 ]School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Author notes

Article Information

Accepted for Publication: March 7, 2023.

Published: May 3, 2023. doi:10.1001/jamanetworkopen.2023.10302

Corresponding Author: Alireza Biglari, MD, PhD, Tehran University of Medical Sciences, Tehran 1419733151, Iran ( abiglari@ 123456sina.tums.ac.ir ).

Author Contributions: Dr Biglari had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Mostafavi and Eybpoosh contributed equally.

Concept and design: Mostafavi, Eybpoosh, Khalili, Salehi-Vaziri, Khamesipour, Jalali, Mansoori, Keramat, Doroud, Omrani, Asadi, Mirjalili, Eugenia Toledo-Romani, Valenzuela-Silva, Verez-Bencomo, Gouya, Emadi-Koochak, Haghdoost, Biglari.

Acquisition, analysis, or interpretation of data: Mostafavi, Eybpoosh, Karamouzian, Khalili, Haji-Maghsoudi, Salehi-Vaziri, Khamesipour, Jalali, Nakhaeizadeh, Sharifi, Keramat, Ghodrati, Javanian, Pouriayevali, Ghasemian, Farshidi, Pourahmad, Ghasemzadeh, Mounesan, Darvishian, Gouya, Haghdoost, Biglari.

Drafting of the manuscript: Mostafavi, Eybpoosh, Karamouzian, Khalili, Haji-Maghsoudi, Salehi-Vaziri, Khamesipour, Jalali, Nakhaeizadeh, Mansoori, Keramat, Ghodrati, Asadi, Pouriayevali, Farshidi, Ghasemzadeh, Eugenia Toledo-Romani, Valenzuela-Silva, Gouya, Biglari.

Critical revision of the manuscript for important intellectual content: Mostafavi, Eybpoosh, Karamouzian, Khalili, Haji-Maghsoudi, Salehi-Vaziri, Jalali, Nakhaeizadeh, Sharifi, Mansoori, Javanian, Doroud, Omrani, Pouriayevali, Ghasemian, Pourahmad, Mounesan, Darvishian, Mirjalili, Verez-Bencomo, Gouya, Emadi-Koochak, Haghdoost, Biglari.

Statistical analysis: Mostafavi, Karamouzian, Haji-Maghsoudi, Salehi-Vaziri, Nakhaeizadeh, Sharifi, Keramat, Darvishian, Eugenia Toledo-Romani, Valenzuela-Silva, Haghdoost.

Obtained funding: Salehi-Vaziri, Jalali, Omrani, Biglari.

Administrative, technical, or material support: Mostafavi, Eybpoosh, Karamouzian, Khalili, Salehi-Vaziri, Jalali, Sharifi, Mansoori, Keramat, Javanian, Doroud, Omrani, Asadi, Pouriayevali, Farshidi, Pourahmad, Ghasemzadeh, Mounesan, Mirjalili, Gouya, Biglari.

Supervision: Mostafavi, Eybpoosh, Karamouzian, Salehi-Vaziri, Khamesipour, Mansoori, Ghodrati, Javanian, Verez-Bencomo, Gouya, Emadi-Koochak, Biglari.

Conflict of Interest Disclosures: Dr Mostafavi is employed by the Pasteur Institute of Iran; he joined Iran's national COVID-19 vaccine committee after the trial's completion. Dr Eybpoosh is employed by the Pasteur Institute of Iran. Dr Salehi-Vaziri is employed by the Pasteur Institute of Iran. Dr Doroud is employed by the Pasteur Institute of Iran. Dr Omrani was the deputy director of the Pasteur Institute of Iran at the time of the study. Mr Asadi is employed by the Pasteur Institute of Iran. Dr Pouriayevali is employed by the Pasteur Institute of Iran. Dr Farshidi became the deputy minister of health and medical education after the trial's completion. Dr Verez-Bencomo reported serving as general director with compensation of the Finlay Vaccine Institute and having a patent pending for WO 2022/073528. Dr Gouya has been the director of the Center for Disease Control of the Ministry of Health of Iran, a members of Iran’s national COVID-19 vaccine, and served as a nonvoting member of the study’s data safety and monitoring board. Dr Biglari is the former director of Pasteur institute of Iran had been the employer of the Pasteur institute of Iran and is a member of the National Committee for the COVID-19 Vaccine. No other disclosures were reported.

Funding/Support: The Pasteur Institute of Iran funded the study.

Role of the Funder/Sponsor: The Pasteur Institute of Iran designed and had role in preparation, conducting and management of the study, and approved the final protocol and manuscript, but had no role in data collection, data analysis/interpretation, and decision to submit the manuscript for publication

Group Information: Members of the Soberana Study Group and all participating centers are presented in Supplement 3.

Data Sharing Statement: See Supplement 4.

Additional Contributions: We thank all the participants who volunteered for this study. We also acknowledge the contributions of the trial executive staff in the target cities. The executive team in the following centers recruited the participants, administered the vaccines, and conducted follow-up visits: Isfahan, Babol, Mazandaran, Zanjan, Hamadan, Kerman, Yazd (Shahid Sadoughi), and Hormozgan University of Medical Sciences. We also thank the data safety and monitoring board: Reza Mosaed, PhD (Iran Food and Drug Administration); Fariba Asghari, MD, PhD (National Committee for Ethics in Biomedical Research); Seyed Mahmoud Masiha Hashemi, PhD, Saeed Hashemi Nazari, MD, PhD, Seyed Alireza Nadji, PhD, and Majid Mokhtari, MD (Shahid Beheshti University of Medical Sciences); Seyed Ali Dehghan Manshadi, MD, Hossein Khalili, PhD, Amir-Hassan Zarnani, PhD (Tehran University of Medical Sciences); and Ghobad Moradi, MD, PhD (Kurdistan University of Medical Sciences). These members received payment outside of salary for these contributions.

Article

Publisher ID: zoi230329

DOI: 10.1001/jamanetworkopen.2023.10302

PMC ID: 10157429

PubMed ID: 37133864

SO-VID: 30b165dc-1290-4ce7-be85-70794ce4aba9

License:

This is an open access article distributed under the terms of the CC-BY License.

History

Date received : 6 October 2022

Date accepted : 7 March 2023

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Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine : A Randomized Clinical Trial

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Key Points

Question

Findings

Meaning

Abstract

Importance

Objective

Design, Setting, and Participants

Interventions

Main Outcomes and Measures

Results

Conclusions and Relevance

Trial Registration

Abstract

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 32

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

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