COV-Iran Barekat & SpikoGen COVID-19 Vaccines
The Effectiveness of Iranian COVID-19 Vaccines
The COV-Iran Barekat (BIV1-CovIran) is an inactivated whole virus particle vaccine manufactured by the Shifa Pharmed Industrial Group. Two shots of 5µg vaccine are administered intramuscularly at a 28-day interval. The virus was sequenced and cultured using a Vero cell manufacturing platform in a biosafety level 3 (BSL-3) facility. Viral particles were inactivated with β-propiolactone. After purification, the inactivated virus particles were sterilised with filtration and formulated with Alhydrogel as an adjuvant.
Preclinical Studies
Preclinical studies on animals demonstrated safety and potency, including guinea pigs, rabbits, mice, and nonhuman primates.
Phase I and II Clinical Trials
Phase I and Phase II clinical trials of the vaccine were conducted as randomised, placebo-controlled, parallel-designed, double-blind trials to evaluate the inactivated whole virus particle vaccine’s safety, tolerability, and immunogenicity BIV1-CovIran. Phase I was carried out in two stages: Stage I included individuals aged 18-50, and Stage II included individuals aged 51-75 years. Phase I study occurred between 29 December 2020 to 4 March 2021 for Stage I and between 15 March 2021 to 9 April 2021 for Stage II. Phase II was carried out between 15 March 2021 to 25 May 2021. During Phase I, 88 participants aged 18-75 were recruited and in Phase II, the vaccine immunogenicity and safety was tested on 280 participants aged 18-75. Briefly, the neutralising antibody titres rose four times or more among 71%, 100% and 83% of participants in Stage I, Stage II and Phase II participants 14-days after the second dose of 5µg-vaccine. During Phase III, 89% of participants with symptomatic COVID-19 were positive for the delta variant, suggesting that the dominant variant was the delta variant during the study.
Phase III Clinical Trials
Phase III clinical trial of the vaccine was conducted between 16 May 2021, to 15 July 2021, in six cities of Iran, including Tehran, Karaj, Mashhad, Shiraz, Isfahan, and Bushehr in predetermined vaccination centres. This randomised, placebo-controlled, double-blind, multicenter Phase III clinical trial was conducted to investigate the efficacy and safety of an inactivated whole virus particle vaccine, BIV1-CovIran, among 20,000 participants aged 18-75 years located in six cities of Iran. During the 90-day follow-up after the second injection, the BIV1-CovIran vaccine showed an overall efficacy of 50.1%, 70.5%, and 83.1% against non-severe, severe (hospitalisation), and critical cases (ICU admission) of COVID-19, respectively. No death cases were reported among the vaccinated participants. The vaccine efficacy against non-severe cases was 91% among participants aged 65 and older.
Vaccine Safety
The findings of Phase I and Phase II suggested that all adverse events were mild or moderate and transient among vaccinated participants, and no vaccine-related serious adverse events were reported. In the Phase III study, among the safety population, a total of 43,003 adverse events were reported among 13,719 participants, with 9,226 (67%) participants in the vaccine group and 4,493 (33%) in the placebo group. The most common adverse event in all three phases was injection site pain.
Publications
Preclinical study of BIV1-CovIran vaccine was published in the Reviews in medical virology journal on 26 October 2021. From clinical studies, Phase I and Phase II studies were submitted on 27 August 2021, which is currently under peer review and will soon be published. In addition to the Phase I and Phase II manuscript, two other papers, including Phase III study protocol and circulating variant during Phase III study, were submitted to the journals and are currently under journal consideration. Phase III study paper is in the submission process.
Relevant articles can be accessed via the following links:
Safety and potency of BIV1-CovIran inactivated vaccine candidate for SARS-CoV-2: A preclinical study
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https://onlinelibrary.wiley.com/doi/10.1002/rmv.2305
Effectiveness of COVID-19 Vaccines in preventing Infectiousness, Hospitalization and Mortality: A Historical Cohort Study Using Iranian Registration Data During Vaccination program
https://www.medrxiv.org/content/10.1101/2022.01.18.22269330v1.full
Emergency Use Authorisation
BIV1-CovIran received emergency use authorisation on July 14th, 2021, by the local regulator. In addition, the manufacturing site meets the authorisation criteria for Good Manufacturing Practice (GMP). Emergency use authorisation by the World Health Organization (WHO) is in process, all requirements are ready, and so far, two meetings have been held by corresponding authorities in WHO.
The SpikoGen vaccine is a recombinant full spike protein vaccine produced by Iranian CinnaGen Co. in collaboration with an Australian company, Vaxine.
CinnaGen Co. is a privately owned bio-pharmaceutical manufacturer and biotech exporter with its own business development team. As with its other partnerships, this collaboration was established independently. Vaxine and CinnaGen have an agreement in place for the technology transfer, manufacturing and distribution of the vaccine.
Manufacturing
CinnaGen is manufacturing the COVID-19 vaccine under the “SpikoGen” trademark in Iran in its EU-GMP certified production facility located in Simindasht Industrial Area, Alborz, Iran.
CinnaGen is prepared for the export of the vaccine to any country in demand.
Clinical Trials
In the Phase II clinical study, immunogenicity factors including seroconversion to specific antibodies also cellular immunity response has been assessed and the results are submitted to the Ministry of Health. Moreover, in Phase III clinical study the rate of COVID-19 infection after the second dose injection of the vaccine has been evaluated and showed that the efficacy of the vaccine is in line with other vaccines and international guidelines.
The Phase III trial program was a randomized, double-arm, double-blind, vaccine-containing clinical trial to evaluate the efficacy and safety of the vaccine on 16,876 volunteers. Subjects were assigned to either vaccine group or placebo group in ratio of 3:1.
For more details about the trial, you can visit the official website of registered clinical trials: ClinicalTrials.gov Identifier: NCT05005559
Safety
SpikoGen is a full spike recombinant protein containing both S1 and S2 subunits and one of the safest vaccines available in Iran. It has been tested on tens of thousands of people, and is proven safe, well tolerated and efficacious. The safety follow-up of the vaccine study will be continued until March 2022.
Emergency Use Authorization
SpikoGen received the Emergency Use Authorization from Iran Food and Drug Administration on 6 October 2021 after submitting its Phase II and interim analysis of Phase III efficacy and safety report, proving to be safe and efficacious. Iranian FDA independently reviewed the data and the efficacy against mild to moderate COVID-19 in PP and seropositive population while the delta variant was dominant over Iran, which was significant. Currently, the vaccine is only approved in Iran, but it is in process of obtaining the World Health Organization EUL/Prequalification.