Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine

Abstract

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

Immunogenicity and Safety of SARS-CoV-2 Protein Subunit Recombinant Vaccine (IndoVac®) as a Booster Dose against COVID-19 in Indonesian Adults

“…A study in Iran showed a different result from our study [15]. The seropositive rate was only 30% after 28 days of the booster dose administration [15]. Other studies have also shown that antibody levels after administration of a booster dose of the mRNA vaccine were higher than after administration of the protein subunit recombinant and viral vector vaccine [22][23][24].…”

“…A heterologous booster study was also conducted for Biological E's Corbevax, another vaccine with a similar platform to IndoVac ® Vaccine, which has been approved by the Indian Regulatory Authority as a heterologous booster for Covishield (ChAdOx1 vaccine) and Covaxin (inactivated vaccine) [21]. A study in Iran showed a different result from our study [15]. The seropositive rate was only 30% after 28 days of the booster dose administration [15].…”

“…In this vaccine design, RBD was formulated with CpG 1018 and aluminium hydroxide adjuvants to effectively induce antibodies that neutralise wild-type live viruses while minimising Th2-biased responses with no vaccine-related AEs [14,15,[17][18][19]. Recombinant protein vaccine containing SARS-CoV-2 RBD elicited a potent immune response, with neutralising antibodies reaching 99% seroconversion, although the response was lower in the group aged ≥65 years compared with the younger group.…”

“…Preclinical animal studies and controlled trials have demonstrated the potential utility of subunit protein vaccines, making them one of the most viable options for resourcelimited settings because they can be stored in refrigerators and distributed easily [14,15]. This study aimed to evaluate the non-inferiority of the immune response of the SARS-CoV-2 neutralising antibody in IndoVac ® to the control vaccine 14 days after administration of the booster dose.…”

Lessons from COVID-19 Pandemic: A Successful Policy and Practice by Pasteur Institute of Iran

“…The clinical trial phase III was conducted in the country in eight cities, and immunization by a three-dose regimen was significantly effective against hospitalization in the Delta variant era. PastoCovac was approved to be administrated to children above three years old, and at the same time, has been evaluated as an effective and safe booster vaccine for all primary vaccines in Iran [ 40 , 41 ] . In several studies carried out by PII (under review data), PastoCovac Plus immunogenicity was assessed among the individuals primarily immunized by two doses of Covaxin (BBV152), ChAdOx1-S, or BBIBP-CorV.…”