Recombinant Adenovirus Type-5 Vectored COVID-19 Vaccine Trial
- Ad5 vectored COVID-19 vaccine is well tolerated and had no severe side effects by day 28.
- Prior immunity to Ad5, which was common, dampens the immunogenic response to the vaccine.
- Immunogenicity does not necessarily entail protection against the disease. Effectiveness studies are ongoing.
What is the short-term safety and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored coronavirus disease 19 (COVID-19) vaccine?
This was a dose-escalation, single-center, open-label, nonrandomized phase 1 trial of 108 healthy participants (51% male, mean age 36 years) with no prior exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), confirmed by the absence of IgM or IgG antibodies, and no evidence of lesions on chest computed tomography. Participants were enrolled sequentially to receive a single intramuscular injection of CanSino’s nonreplicating adenovirus type-5 (Ad5) vectored COVID-19 vaccine. The first group of participants (n = 36) received a low dose (5 × 10¹⁰ viral particles), the second group (n = 36) received a medium dose (1 × 10¹¹ viral particles), and the last group (n = 36) received a high dose (1.5 × 10¹¹ viral particles). The primary endpoint for safety was the occurrence of adverse reactions within 7 days after the vaccination. Abnormal laboratory measures and adverse events within 28 days were analyzed as secondary endpoints. The primary endpoint for immunogenicity was antibody responses to the receptor binding domain (RBD) and spike glycoprotein of SARS-CoV-2.
Approximately 80% of participants reported at least one adverse reaction within the first 7 days after vaccination. The most common adverse reactions were pain (54%), fever (46%), fatigue (44%), headache (39%), and muscle pain (17%). Most adverse reactions were mild or moderate in severity. There was no difference in the reporting of adverse reactions between groups. No serious adverse event was reported within 28 days. Mild elevation in total bilirubin and alanine aminotransferase were noted (8%), none considered clinically significant. Rapid binding antibody responses to RBD were observed in all three dose groups, with the high-dose group tending to have a higher binding antibody titer. At least a four-fold increase of anti-RBD antibodies was noted in ≥94% of participants in all three groups. Neutralizing antibody titers peaked at 28 days post-vaccination, with a stepwise increase according to vaccine dose. Pre-existing immunity to Ad5 was common and attenuated the increase in neutralizing antibody. Recipients aged 45–60 years had lower seroconversion rates compared to younger participants. T-cell responses were noted in recipients and peaked at 14 days post-vaccination.
The Ad5 vectored COVID-19 vaccine is well tolerated and immunogenic at 28 days post-vaccination.
This report is the first of an in-human vaccination trial for COVID-19 using the Ad5 vector, which focuses on tolerability, short-term adverse effects, and immunogenicity. A single dose of the vaccine was able to elicit a four-fold increase in neutralizing antibodies in 50-75% of participants, with activation of both CD4 and CD8 T-cell responses. These responses however are often temporary, and heavily attenuated by pre-existing Ad5 immunity, which was common in this cohort. Whether such a response is adequately protective against COVID-19 still needs to be determined, in addition to long-term safety of the vaccine.
Keywords: Adenoviridae, Adenoviridae Infections, Alanine Transaminase, Antibodies, Neutralizing, Bilirubin, Coronavirus, Coronavirus Infections, COVID-19, Coronavirus Infections, COVID-19, D-Alanine Transaminase, Fever, Injections, Intramuscular, Myalgia, Primary Prevention, SARS Virus, severe acute respiratory syndrome coronavirus 2, Tomography, X-Ray Computed
< Back to Listings