Research in context
Evidence before this study
We searched PubMed on July 16, 2020, for clinical trial reports with the terms “COVID-19” or “SARS-CoV-2”, “vaccine”, and “clinical trial”. Using the same terms, we also searched ClinicalTrials.gov
for unpublished trials of COVID-19 vaccines. Except for the results of our earlier phase 1 study with the adenovirus type-5 (Ad5)-vectored vaccine and a phase 1 clinical trial with an mRNA vaccine (mRNA-1273) done in a small number of participants, no other COVID-19 vaccine data from clinical trials have been reported. We found registered trials with 11 candidate COVID-19 vaccines at ClinicalTrials.gov
, including three recombinant protein-based vaccines, two viral vector-based vaccines, one DNA vaccine, two mRNA vaccines, two inactivated virus vaccines, and one autologous dendritic cell-based vaccine loaded with antigens from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The majority of the trials registered were in early phases; only ChAdOx1 nCoV-19 developed by the University of Oxford (Oxford, UK) is going to be evaluated in a phase 3 trial.
In the previously reported open-label, non-randomised, phase 1 trial, we found that the Ad5-vectored COVID-19 vaccine was tolerable and immunogenic in healthy adults. One dose of the vaccine induced rapid specific T-cell and humoral responses by 14 days.
Added value of this study
This study provides more evidence for the immunogenicity and safety of the Ad5-vectored COVID-19 vaccine in a larger population. To assess the vaccine in a more diverse population, we removed the age cap for the recruitment of participants for this phase 2 trial. Older individuals (ie, aged ≥55 years), many of whom often have chronic illness, have a high risk of serious illness and death associated with SARS-CoV-2 infection; thus, they are an important target population for a COVID-19 vaccine. Our results suggest a single-dose immunisation schedule of Ad5-vectored COVID-19 vaccine at 5?×?1010 viral particles is an appropriate regimen for healthy adults. Compared with the younger population, we found older people to have a significantly lower immune response, but higher tolerability, to the Ad5-vectored COVID-19 vaccine. Therefore, an additional dose might be needed to induce a better immune response in the older population, and this will be evaluated in a phase 2b trial.
Implications of all the available evidence
Evidence from this phase 2 study indicates the candidate Ad5-vectored COVID-19 vaccine has a good safety profile, with only mild, transient adverse events related to vaccination and no serious adverse events. Single-dose immunisation with the vaccine induced rapid onset of immune responses within 14 days and significant humoral and cellular immune responses within 28 days in the majority of the recipients. We are planning an international multicentre, randomised, double-blind, controlled phase 3 effectiveness trial to further evaluate the efficacy of the vaccine. We are in the midst of a global COVID-19 pandemic; thus, timely sharing of the results of clinical trials with candidate vaccines is critical. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext
By Roman Ribnikov especially for Medical Express