ABSTRACT
Background: Heterologous orally administered adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in individuals who were primed with two-dose CoronaVac (an inactivated SARS-CoV-2 vaccine, by Sinovac) previously, has been reported to be safe and highly immunogenic within 28 days post-boosting. However, antibody persistence and safety up to 6 months of this regimen are not been reported yet. Methods: This is a randomized, open label, single-center trial on safety and immunogenicity of heterologous boost immunization with an orally administered aerosolised Ad5-nCoV vs. homologous boost immunization with CoronaVac after two-dose priming with CoronaVac in Chinese adults aged 18 years and older (NCT05043259). We followed the participants in this trial, including 140 in the low-dose aerosolised Ad5-nCoV group, 139 in the high-dose aerosolised Ad5-nCoV group, and 140 in the CoronaVac group for 6 months. Neutralising antibodies (NAbs) against live wild-type SARS-CoV-2 virus and omicron variant, and receptor-binding domain (RBD)-specific IgG antibodies were detected in serum samples collected at 28 days, 3 months, and 6 months after the booster dose. Serious adverse events (SAEs) were documented till month 6. Results: The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 1937.3 [95% CI 1466.9, 2558.4] and 1350.8 [95% CI 952.6, 1915.3], which were 26.4 folds and 18.4 folds higher than that the CoronaVac group did (73.5 [95%CI 52.3, 103.3]) at 28 days. The low-dose and high-dose heterologous boost immunisation groups had NAb GMTs against live wild-type SARS-CoV-2 of 530.1 (95% CI 412.5, 681.1) and 457.6 (95%CI 349.4, 599.2), which were 26.0 folds and 22.4 folds higher than that the CoronaVac group did (20.4 [95%CI 14.3, 29.1]) at 3 months, respectively. At 6 months, the low-dose and high-dose heterologous booster groups had NAb GMTs against live wild-type SARS-CoV-2 of 312.9 (95%CI 237.7, 411.8) and 251.1 (95%CI 178.2, 354.0), which were 30.1 folds and 24.1 folds higher than the CoronaVac group did (10.4 [95%CI 7.8, 14.0]), respectively. Additionally, the low-dose and high-dose heterologous booster groups had NAb GMTs against live omicron variant of 52.0 (95%CI 37.2, 72.6) and 23.1 (95%CI 15.7, 33.9) at 28 days, 27.9 (95% CI 18.8, 41.3) and 23.3 (95%CI 16.2, 33.3) at 3 months, 16.0 (95%CI 10.9, 23.5) and 12.0 (95%CI 8.5, 16.8) at 6 months, respectively. However, nearly all participants had no detectable NAbs for omicron variant in the CoronaVac group at either 28 days, 3 months, or 6 months. No vaccine-related SAEs were observed. Conclusions: These data suggested that heterologous aerosolised Ad5-nCoV following two-dose CoronaVac priming was safe and persistently more immunogenic than three-dose CoronaVac, although immune responses waned over time.
Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse ReactionsABSTRACT
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 (1:1) 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