Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine
Authors: Mostafavi Ehsan , Eybpoosh Sana , Karamouzian Mohammad , Khalili Malahat , Haji-Maghsoudi Saiedeh , Salehi-Vaziri Mostafa , Khamesipour Ali , Jalali Tahmineh , Nakhaeizadeh Mehran , Sharifi Hamid , Mansoori Yasaman , Keramat Fariba , Ghodrati Samad , Javanian Mostafa , Doroud Delaram , Omrani Mir Davood , Asadi Hassan , Pouriayevali Mohammad Hassan , Ghasemian Roya , Farshidi Hossein , Pourahmad Morteza , Ghasemzadeh Iman , Mounesan Leila , Darvishian Maryam , Mirjalili Mohamad Reza , Toledo-Romani Maria Eugenia , Valenzuela-Silva Carmen , Verez-Bencomo Vicente , Gouya Mohammad Mehdi , Emadi-Koochak Hamid , Haghdoost Ali Akbar , Biglari Alireza ,   Soberana Study Group, Soleimani Tappeh Sari Behnaz , Ebrahimpour Soheil , Heydar Tabar Rostam , Vaseghi Roghayye , Mirzaei Bahram , Safarpour Mehdi , Sadeghi Farzin , Hosseinpoor Mahmoud , Raznahan Tayebeh , Haddadi Leila , Mobarak Abadi Arezoo , Khalili Elham , Manaei Mehrsa , Morshedi Hassan , Gooklani Hamed , Karami Manouchehr , Khazaei Mohammad  , Bathaei Seyyed Jalaleddin , Ataei Ali , Zahiri Ali , Eskandari Zahra  , Karbalaei Zadeh Firouzeh , Abdoli Elham , Arjmandian Marzieh , Zamanian Maryam , Sadat Mirmoeini Razieh , Hashemi Seyyede Zeinab , Azizi Jalilian Farid , Heidari Kamal , Farsi Mehdi , Mostajeran Mahnaz , Mashkooti Marjan , Davashi Somayye , Kian Poor Nastaran , Haddadpour Asefeh , Mazrooei Fariba , Safizadeh Hossein , Naghavi Mohammadreza , Sohbati Saeed , Mohit Kermani Nadia , Nasiri Moghaddam Nasim , Dabiri Shahriar , Oveis Ghasem , Parsaei Mohammadreza , Khalizadeh Maghsood , Arjmand Abbas , Yazdi Zadeh Fatemeh , Dehbashi araghdari Hadi , Bandalizadeh Zainab , Dehghani Mohammadreza , Mansouri Mehrdad , Sharifi Masoud , Shojaei Far Hossein , Soheili Javad , Owlia Sina , Mazidi Masoumeh , Sharif Yazdi Mohammad , Bahri Mahdieh , Hashemi Razieh Sadat , Talebi Alireza , Anvari Saeideh , Jafari Ahmad , Saeini Mohammadreza , Najafi Fariba , Rahmani Davoud , Seidy Ali , Hajikhani Mahshid , Dinmohammadi Hossein , Javadi Amir , Eskandari Seyed Ebrahim , Handjani Farhad , Chegeni Maryam , Seif Farahi Katayoun , Hemmati Payman , Tavakoli Rad Mahsa , Fereidooni Zahra , Khakifirouz Sahar , Mohammadi Tahereh , Fazlalipour Mehdi , Maleki Ali , Nemati Amir Hesam , Ghasemi Ahmad , Azad Manjiri Sanam , Ahmadi Zahra , Yekta Sanati Parastoo , Kashanian Setareh , Mortazavipoor Mohammad Mehdi , Farhan Asadi Laya , Hosseini Zahra , Niknam Oskouei Farideh , Gerdooie Sepideh , Sajadi Marzyie , Rostamtabar Maryam , Sabouni Talieh , Rahimi Alireza , Kavianpour Alireza , Zahraei Seyed Mohsen , Tayeri Katayoun , Asadollahi Amin Ali ,  Tohidinik Hamid Reza , Rastegari Azam , Mehmandoost Soheil 
Published: May 2023

ImportanceThe 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.ObjectiveTo 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 ParticipantsA 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.InterventionsIn 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 MeasuresThe 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.ResultsIn 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 RelevanceIn 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 Registrationisrctn.org Identifier: IRCT20210303050558N1