A recombinant adenovirus type 5 vectored vaccine against coronavirus disease 2019 (COVID-19) was found to be well tolerated and immunogenic, according to phase 1 study results published in The Lancet.
The dose-escalated, non-randomized, open-label study was conducted at a single center in Wuhan, China. “We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain,” the study authors explained.
A total of 108 healthy adult volunteers 18 to 60 years old (mean age, 36.3 years old) with no history of COVID-19 infection were enrolled in the study. Each patient was allocated to 1 of 3 dose groups and received a single intramuscular injection of the vaccine. The primary end point of the study was adverse events that occurred within 7 days post-vaccination; safety was examined over the 28 day period after the vaccine was administered.
“Specific antibodies were measured with ELISA, and the neutralizing antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralization and pseudovirus neutralization tests,” the authors explained. “T cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays,” they added.
The study authors reported that 83% (30/36) of patients in the low and middle dose groups and 75% (27/36) of patients in the high dose group reported experiencing at least 1 adverse event within 7 days of receiving the vaccine. The most commonly reported injection site adverse reaction was pain, which occurred in 54% (58/108) of vaccine recipients.
Systemic adverse reactions most commonly reported included fever (46%, 50/108), fatigue (44%, 47/108), headache (39%, 42/108), and muscle pain (17%, 18/108). The majority of adverse reactions were considered to be mild or moderate in severity and no serious adverse events occurred within 28 days post-vaccination.
The study authors also reported observing a significant increase in ELISA antibodies as well as neutralizing antibodies 14 days post-vaccination. At day 28, most of the participants had a 4-fold increase in binding antibodies, in addition to a positive T cell response and detectable neutralizing antibodies. However, the authors noted that in participants with high pre-existing immunity to adenovirus type 5, the positive antibody and T cell response was reduced.
“This result shows a promising vision for the development of COVID-19 vaccines, but we are still a long way from this vaccine being available to all,” said Professor Wei Chen from the Beijing Institute of Biotechnology in Beijing, China, one of the authors of the study. To further confirm the findings, a phase 2, randomized, double-blind, placebo-controlled study has been initiated in Wuhan. The trial will enroll 500 healthy adults and will also include participants over 60 years old.
Zhu FC, Li YH, et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial [published online May 22, 2020]. The Lancet. doi: org/10.1016/S0140-6736(20)31208-3.