Safety and immunogenicity of heterologous COVID-19 vaccine regimens to deal with product shortage: A randomised clinical trial in an elderly population.

Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.