May 25, 2020

First published human data for COVID-19 vaccine find it “tolerable and immunogenic”

Results from a first-in-human trial published in The Lancet for a recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine showed that the vaccine candidate was tolerable and immunogenic in healthy adults.

“Specific humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination, and rapid, specific T-cell responses were noted from day 14 after one shot of the vaccine”, Professor Feng-Cai Zhu, Jiangsu Provincial Center for Disease Control and Prevention, China, and colleagues wrote. The authors added that there is potential for further investigation of the Ad5-vectored COVID-19 vaccine for the control of the COVID-19 outbreak.

The authors conducted a single-centre, open-label, non-randomised, dose-escalation Phase 1 trial of the vaccine candidate in a rehabilitation centre in Wuhan, Hubei province, China. Eligible participants were healthy adults aged between 18 and 60 years, who did not have SARS-CoV-2 infection.

A total of 108 eligible individuals were enrolled in the trial and were assigned to receive intramuscular injection of the Ad5 vectored COVID-19 vaccine either at a low dose (5 × 1010 viral particles per 0·5 mL; 36 patients), middle dose (1 × 1011 viral particles per mL; 36 patients), or high dose (1·5 × 1011 viral particles per 1·5 mL; 36 patients). Blood samples were taken from participants for serology tests at the scheduled site visits before the vaccination, and on days 14 and 28 after the vaccination.

The primary endpoint for safety was the occurrence of adverse reactions within 7 days after the vaccination. Any abnormal changes in laboratory measures at 7 days post-vaccination, and adverse events within 28 days across the treatment groups were also analysed as secondary safety endpoints. 

The study showed that 87 (81%) of 108 participants reported at least one adverse reaction within the first 7 days after the vaccination: 30 (83%) in the low dose group, 30 (83%) in the middle dose group, and 27 (75%) in the high dose group. 

The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients. The most commonly reported systemic adverse reactions overall were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]). Most adverse reactions were mild or moderate in severity. Nine participants (8%) had an episode of severe fever (grade 3) with axillary temperature greater than 38·5°C. Of them, one from the high dose group reported severe fever along with severe symptoms of fatigue, dyspnoea, and muscle pain. One participant in the high dose group reported severe fatigue and joint pain. These reactions occurred within 24 hours post-vaccination, and persisted for no more than 48 hours. The authors reported no significant difference in the incidences of adverse reactions or overall adverse events among the dose groups. 

The authors reported that ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.

Rapid binding antibody responses to receptor binding domain (RBD) were observed in all three dose groups from day 14. At least a four-fold increase of anti-RBD antibodies was noted in 35 (97%) participants in the low dose group, 34 (94%) in the middle dose group, and 36 (100%) in the high dose group by day 28. 

Neutralising antibodies against live SARS-CoV-2 were all negative at day 0, and increased moderately at day 14, peaking at 28 days post-vaccination. By day 28, 18 (50%) participants in the low dose group, 18 (50%) in the middle dose group, and 27 (75%) in the high dose group had at least a four-fold increase in neutralising antibody titres. 

High proportions of participants with positive T-cell responses were reported across all dose groups post-vaccination. The activation of both CD4+ T cells and CD8+ T cells was observed in vaccine recipients, particularly for antigen-specific CD4+ T cells and CD8+ T cells. 

“However, both the specific antibody response and T-cell response induced by vaccination were partly diminished by the presence of high pre-existing anti-Ad5 immunity”, the authors wrote. 

“Our study found that the pre-existing Ad5 immunity could slow down the rapid immune responses to SARS-CoV-2 and also lower the peak of the responses, particularly for humoral immunity. The high pre-existing Ad5 immunity might also have a negative effect on the persistence of the vaccine-elicited immune responses”, they added. 

The authors noted that the main limitations of the trial are the small size of the cohort, the short duration of follow-up, and the absence of a randomised control group.

“An ongoing Phase II trial in China will provide more information on the safety and immunogenicity of the Ad5 vectored COVID-19 vaccine”, the authors added.

SOURCE: The Lancet