Heterologous CoronaVac plus Ad5-nCOV versus homologous CoronaVac vaccination among elderly: a phase 4, non-inferiority, randomized study
Authors: Jin Pengfei , Li Jingxin , Guo Xiling , Gou Jinbo , Hou Lihua , Song Zhizhou , Zhu Tao , Pan Hongxing , Zhu Jiahong , Shi Fengjuan , Du Pan , Huang Haitao , Liu Jingxian , Zheng Hui , Wang Xue , Chen Yin , Wan Peng , Wu Shipo , Wang Xuewen , Xu Xiaoyu , Chen Wei , Zhu Fengcai 
Published: June 2022

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 older, of 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

ClinicalTrials.govNCT04952727

Key Points

Question

Does a heterologous immunization with recombinant adenovirus type 5-vectored vaccine (Convidecia) produced a non-inferior or superior response of neutralizing antibodies among elderly primed with two doses of inactivated COVID-19 vaccine (CoronaVac), compared to the homologous boosting

Findings

In this randomized clinical trial, a heterologous third dose of Convidecia resulted in a 6.2-fold (geometric mean titers: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against wild-type strain, Delta and Omicron variants 14 days post boosting, respectively, compared to the homologous boost with CoronaVac

Meaning

Heterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boosting.