Safety and Immunogenicity of an Inactivated Whole Virion SARS-CoV-2 Vaccine, TURKOVAC, in Healthy Adults: Interim Results from Randomised, Double-Blind, Placebo-Controlled Phase 1 and 2 Trials

Abstract

Background: Safe and effective vaccine options is crucial to fight against COVID-19 pandemic. We report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine.

Methods: Double-blind, randomised, single centre, phase 1&2 trials included SARS-CoV-2 seronegative healthy adults aged 18-55 years (18-64 in phase 2). Participants, were assigned to receive two intramuscular doses of ERUCoV-VAC 3µg or 6µg or placebo 21 days apart (28 days in phase 2) via computer-generated randomisation. Primary endpoints: number (percentage) of participants experiencing adverse events (AEs) within 43 days of first vaccination in phase 1 and SARS-CoV-2 neutralising antibody titres and seroconversion rates on day 43 in phase 2 trials. (ClinicalTrials.gov: phase 1, NCT04691947; phase 2, NCT04824391).

Findings: Forty-four participants (3µg [n=17], 6µg [n=17], placebo [n=10]) in phase 1 and 250 (3µg [n=100], 6µg [n=100], placebo [n=50]) in phase 2 received ≥1 dose. Until day 43, 25 Aes (80% mild) occurred in 15 (34.1%) participants in phase 1, and 268 Aes (67.2% moderately severe) occurred in 153 (61.2%) participants in phase 2. The most common Aes were injection site pain (9/44; 20.5%) in phase 1, and headache (56/47; 18.8%) in phase 2. Vaccine groups were similar in inducing SARS-CoV-2 wild-type neutralising antibody (MNT₅₀): GMTs (95%CI) were 30.0 (37.9-22.0) vs. 34.9 (47.6-22.1) at day 43 (p=0.0666). FRNT50 confirmed MNT₅₀ results: 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p=0.3366). Seroconversion rates (95%CI) were 95.7% (91.4-99.8) vs. 98.9% (96.9-100.0) at day 43 (p=0.8710) in ERUCoV-VAC 3µg and 6µg groups, respectively.

Interpretation: Two-doses of ERUCoV-VAC 3μg and 6μg 28 days apart had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95% at day 43 after first vaccination.

Note:
Funding Information: Both phase 1 and phase 2 studies were funded by the Health Institutes of Turkiye (TUSEB) and Erciyes University.

Conflict of Interests: Aykut Ozdarendeli, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Muhammet Ali Uygut and Gunsu Aydin are the named inventors on patent applications covering inactivated COVID-19 vaccine development.

Ethical Approval: Studies were approved by the Ethics Committee for Clinical Trials of Erciyes University and Turkish Ministry of Health (2020/548, October 28, 2020 for phase 1 and 2021/74, February 01, 2021 for phase 2).

Trial Registration: Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391).

Keywords: ERUCoV-VAC, TURKOVAC, Inactivated whole virion vaccine, COVID-19, SARS-CoV-2