Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia

Abstract

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 14 703 with the frozen formulation and 11 143 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...

Prime-boost vaccination of mice and Rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates

“…1D). However, the pre-existing anti-Ad5 immunity might partly limit vaccine effectiveness, especially for populations aged over 50 ( 8,9,24,25 ), while the low seroprevalence of antibodies to novel adenoviral vectors such as ChAdox1 ( 11 ), Ad26 ( 12,14,21,27 ), and Sad23L and Ad49L used in this study might avoid a negative impact on vaccine efficacy ( 22–24 ).…”

“…A safe and effective COVID-19 vaccine is one of the most wanted goods in the world. Among 33 COVID-19 candidate vaccines in clinical trials (WHO report on 28 August 2020) ( 6 ), 9 vaccines have initiated clinical phase III trial, and experimental data from pre-clinical and/or clinical studies have been published ( 8–21 ). In the frontline of COVID-19 vaccine candidates in clinical trial phase III, the range of approaches includes three inactivated virus, two lipid nanoparticle (LNP)-encapsulated mRNA and four non-replicating adenovirus vectored vaccines ( 6 ).…”

“…The vectors Sad23L and Ad49L originated from simian adenovirus type 23 and human adenovirus type 49, respectively ( 22, 23 ), are novel adenoviral vector. Comparing Ad5-vectored COVID-19, ChAdox1 nCoV-19 and Ad26.COV2.S vaccines ( 8-12,14,21 ), three attractive aspects emphasized in this study are highlighted below.…”

“…However, relatively weaker protection in animals and lower immune response in humans were observed with a single dose of vaccine compared with prime-boost immunizations by two or three doses of inactivated virus or mRNA vaccines ( 15–19 ). Enhancement of immune response was evidenced by prime and boost vaccination regimens with homologous boosting of ChAdOx1 nCoV-19 in animals and humans ( 11, 20 ), or with heterologous Ad26 and Ad5 vectored COVID-19 vaccines in humans ( 21 ).…”

Seven days in medicine: 2-8 September 2020

“…No serious adverse events were detected in two small, early phase trials of the Russian Sputnik V vaccine among 76 people aged 18 to 60 who were followed for 42 days, Russian researchers reported in the Lancet 1. Participants received the frozen or freeze dried version of either one dose or two doses (21 days apart) of the two part vaccine composed of recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S).…”