Summary
Background
We developed a heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type  26  (rAd26)  vector  and  a  recombinant  adenovirus  type  5  (rAd5)  vector,  both  carrying  the  gene  for  severe  acute  respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (rAd26-S and rAd5-S). We aimed to assess the safety and immunogenicity of two formulations (frozen and lyophilised) of this vaccine.
Methods
We did two open, non-randomised phase 1/2 studies at two hospitals in Russia. We enrolled healthy adult volunteers  (men  and  women)  aged  18–60  years  to  both  studies.  In  phase  1  of  each  study,  we  administered  intramuscularly  on  day  0  either  one  dose  of  rAd26-S  or  one  dose  of  rAd5-S  and  assessed  the  safety  of  the  two components for 28 days. In phase 2 of the study, which began no earlier than 5 days after phase 1 vaccination, we  administered  intramuscularly  a  prime-boost  vaccination,  with  rAd26-S  given  on  day  0  and  rAd5-S  on  day  21.  Primary outcome measures were antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA on days 0, 14, 21, 28, and 42) and safety (number of participants with adverse events monitored throughout the study).  Secondary  outcome  measures  were  antigen-specific  cellular  immunity  (T-cell  responses  and  interferon-γ  concentration) and change in neutralising antibodies (detected with a SARS-CoV-2 neutralisation assay). These trials are registered with ClinicalTrials.gov, NCT04436471 and NCT04437875.
Findings
Between June 18 and Aug 3, 2020, we enrolled 76 participants to the two studies (38 in each study). In each study,  nine  volunteers  received  rAd26-S  in  phase  1,  nine  received  rAd5-S  in  phase  1,  and  20  received  rAd26-S  and  rAd5-S in phase 2. Both vaccine formulations were safe and well tolerated. The most common adverse events were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint  pain  (18  [24%]).  Most  adverse  events  were  mild  and  no  serious  adverse  events  were  detected.  All  participants  produced antibodies to SARS-CoV-2 glycoprotein. At day 42, receptor binding domain-specific IgG titres were 14703 with the frozen formulation and 11143 with the lyophilised formulation, and neutralising antibodies were 49·25 with the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+with  the  frozen  formulation,  and  a  median  cell  proliferation  of  1·3%  CD4+  and  1·1%  CD8+  with  the  lyophilised  formulation.
Interpretation
The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants. Further investigation is needed of the effectiveness of this vaccine for prevention of COVID-19.