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: Development of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 tri-als of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine.Methods: Double-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronega-tive healthy adults aged 18-55 years (18-64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 mu g or 6 mu g unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 mu g or 6 mu g (an inactivated vaccine contain-ing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer -generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391).Results: Forty-four participants (3 mu g [n:17], 6 mu g [n:17], placebo [n:10]) in phase 1 and 250 (3 mu g [n:100], 6 mu g [n:100], placebo [n:50]) in phase 2 received >= 1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most com-mon AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 mu g and 6 mu g groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4-10.3) vs. 8.6 (7.0- 10.2) at day 43 (p = 0.7357) and 9.7 (6.0-13.4) vs. 10.8 (8.8-12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3-10.5) vs. 9.0 (7.2-10.8) at day 43 (p = 0.5393) and 11.0 (7.0-14.9) vs. 12.3 (10.3-14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5-98.3) vs 94.1 % (71.3-99.8) at day 43 (p = 0.8727) and 92.8 % (66.1-99.8) vs. 100 % (79.4-100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 mu g and 6 mu g groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 mu g and 6 mu g groups were comparable 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) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p = 0.3366) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 % CI) were 95.7 % (91.4-99.8) vs. 98.9 % (96.9-100.0) at day 43 (p = 0.8710) and 96.6 % (92.8-100.0) vs 98.9 % (96.7-100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 mu g and 6 mu g groups, respectively.Conclusions: Two-dose regimens of ERUCoV-VAC 3 mu g and 6 mu g 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).