1. The novel SARS-CoV-2 vaccine, ChAdOx1 nCoV-2, offered a reasonable safety profile with no serious adverse events in first phase 1/2 trial.
2. ChAdOx1 nCoV-2 showed neutralizing antibody responses against SARS-CoV-2 in the majority of patients.
Evidence Rating Level: 1 (Excellent)
Study Rundown: No vaccines have been approved for the prevention of COVID-19 to date. Replication-deficient viral vectored ChadOx1 vaccines have shown good safety and immunogenic profiles in immunocompromised and elderly individuals, respectively, and stand as a promising candidate for a SARS-CoV-2 vaccine. This phase 1/2 single-blind, randomized controlled trial tested the safety and immunogenicity of the novel ChAdOx1 nCoV-2 vaccine, a replication-deficient simian adenovirus-based vaccine which has previously shown efficacy in rhesus macaques, in a sample of healthy adults. Overall, ChAdOx1 nCoV-2 showed more adverse events than the comparator vaccine, MenACWY; however, there were no serious adverse events in the ChAdOx1 nCoV-2 arm, and administration of prophylactic paracetamol significantly reduced most adverse events. Antibodies against SARS-CoV-2 spike protein increased in the ChAdOx1 nCoV-2 arm by 28 days, and all those exposed to SARS-CoV-2 exhibited neutralizing antibody responses. Important limitations of this study include the relatively short follow-up, single-blinded design, and limited generalizability; most participants were young, healthy and Caucasian. However, given the promising safety, tolerability and immunogenicity profiles of the ChAdOx1 nCoV-2 vaccine, testing for efficacy and safety in older adults and the development of phase 2 and 3 trials are certainly merited.
Click to read the study in The Lancet
In-Depth [randomized controlled trial]: This two-arm, phase 1/2, participant-blinded, multicenter, randomized controlled trial was conducted in five centers across the United Kingdom, and enrolled a total of 1077 participants, divided evenly between both arms. The comparator was the meningococcal conjugate vaccine MenACWY, chosen for its similar adverse event profile. Participants were aged 18 to 55 years old, and were excluded if any of the following were present: history of confirmed SARS-CoV-2, at higher risk for SARS-CoV-2 exposure (e.g., frontline healthcare worker) and those with new-onset symptoms consistent with COVID-19 (fever, cough, etc.). The median age was 35 years (interquartile range [IQR] 28 to 44 years) and 536 (49.8%) were female; 979 (90.9%) participants were Caucasian. The first co-primary endpoint was the safety of the ChAdOx1 nCoV-2 vaccine as measured by serious adverse events, and the second co-primary endpoint was the vaccine’s efficacy as measured by symptomatic, confirmed COVID-19 cases. Although adverse events were more common in the ChAdOx1 nCoV-2 group (e.g., 70% of participants reported fatigue versus 48% in the comparator arm), no serious adverse events were experienced in the former, and adverse reaction rates showed significant reductions with prophylactic paracetamol. Antibodies against SARS-CoV-2 spike protein reached maximal levels by day 28 (median 157 ELISA units, IQR 96 to 317; n=127) and remained high until day 56 (119 ELISA units, 70 to 203; n=43). Using the plaque reduction neutralization test, 35 participants in contact with SARS-CoV-2 (100%) achieved neutralizing titres (median titre 218, IQR 122 to 395); prophylactic paracetamol had no effect on immunogenicity of this vaccine. In summary, the novel ChAdOx1 nCoV-2 single-dose vaccine offered a promising safety and immunogenicity profile in preliminary investigations, meriting further investigation in older adults and with larger-scale phase 2 and 3 trials.
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