Heterologous CoronaVac plus Ad5-nCOV versus homologous CoronaVac vaccination among elderly: a phase 4, non-inferiority, randomized study (preprint)

ABSTRACT

Importance People over 60 developed less protection after two doses of inactivated COVID-19 vaccine than younger people. Heterologous vaccination might provide greater immunity and protection against variants of concern. Objective To assess the safety and immunogenicity of a heterologous immunization with an adenovirus type 5-vectored vaccine (Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. Design An observer-blind, randomized (11) trial, conducted from August 26 to November 13, 2021. Setting A single center in Jiangsu Province, China. Participants 299 participants aged 60 years and olderof them 199 primed with two doses of CoronaVac in the past 3-6 months and 100 primed with one dose of CoronaVac in the past 1-2 months. Intervention Convidecia or CoronaVac as boosting dose Main Outcomes and Measures Geometric mean titers (GMTs) of neutralizing antibodies against wild-type SARS-CoV-2, and Delta and Omicron variants 14 days post boosting, and adverse reactions within 28 days. Results In the three-dose regimen cohort (n=199; mean (SD) age, 66.7 (4.2) years; 74 (37.2%) female), 99 and 100 received a third dose of Convidecia (group A) and CoronaVac (group B), respectively. In the two-dose regimen cohort (n=100; mean (SD) age, 70.5 (6.0) years; 49 (49%) female), 50 and 50 received a second dose of Convidecia (group C) and CoronaVac (group D), respectively. GMTs of neutralizing antibodies against wild-type SARS-CoV-2 at day 14 were 286.4 (95% CI 244.6, 335.2) in group A and 48.2 (95% CI 39.5, 58.7) in group B, with GMT ratio of 6.2 (95% CI 4.7, 8.1), and 70.9 (95% CI 49.5, 101.7) in group C and 9.3 (95% CI 6.2, 13.9) in group D, with GMT ratio of 7.6 (95% CI 4.1, 14.1). There was a 6.3-fold (GMTs, 45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against Delta and Omicron variants in group A, respectively, compared with group B. However, there was no significant difference between group C and group D. Both heterologous and homologous booster immunizations were safe and well tolerated. Conclusions and Relevance Heterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boost, without increasing safety concerns. Trial Registration Clinical Trials.gov NCT04952727