Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial
RCT in 508 healthy adults in Wuhan found 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, with a good safety profile.
Source:
The Lancet
SPS commentary:
This study was conducted by investigators from Wuhan with support from CanSino Biologics. It is one of two early phase COVID-19 vaccine trials reported in the Lancet. The other study was conducted at the Jenner Institute at Oxford University, with support from AstraZeneca.
The UK study evaluated a chimpanzee adenovirus-vectored vaccine in 1077 healthy adults and showed acceptable safety profile, and boosting increased antibody responses compared with meningococcal conjugate vaccine (MenACWY) as control. Humoral responses to SARS-CoV-2 spike protein peaked by day 28 post prime and cellular responses were induced in all participants by day 14. Neutralising antibodies were induced in all participants after a second vaccine dose. After two doses, potent cellular and humoral immunogenicity was present in all participants studied.
Both groups used an adenoviral vector, and both report the vaccine achieving humoral responses to the SARS-CoV-2 spike glycoprotein receptor binding domain by day 28 as well as T-cell responses. Both report local and systemic mild adverse events such as fever, fatigue, and injection site pain. In neither trial was a severe adverse event reported.
A commentary notes that data from these hugely anticipated trials augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety. It adds that overall, the results of both trials are broadly similar and promising, notwithstanding differences in the vector, in the geographical locations of the populations studied, and the neutralisation assays used. Furthermore, without drawing causal inference, the exploration of associations of age and sex with adverse events and immunogenicity reported in Chinese study, and of longevity of response by in British study, are welcomed, given the differential burden of severe outcomes in older adults, and the emerging science around differential sex-specific vaccine effects. It stresses that these COVID-19 vaccine trials are small so inferential caution is warranted, but the explorations are laudable. It concludes that the success of COVID-19 vaccines hinges on community trust in vaccine sciences, which requires comprehensive and transparent evaluation of risk and honest communication of potential harms. Along with the trajectory of vaccine study, it calls for urgent pharmacovigilance, including surveillance for asymptomatic infection among vaccinated and unvaccinated persons if both absolute and relative risk of adverse vaccine outcomes, such as enhanced disease, are to be determined.