Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij‐Rammerstorfer, Sandra; Wright, Daniel; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W.P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna B.; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valérie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles W.; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa

doi:10.1038/s41541-020-00221-3

Cited by 127 publications

(135 citation statements)

References 25 publications

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“…These are typically based on another virus that has been engineered to express the S and has been disabled from replication in vivo by deletion of parts of its genome. The majority of these approaches are based on adenovirus (AdV) vectors but modified vaccinia Ankara, human parainfluenza virus vectors, influenza virus, andeno-associated virus (AAV) and Sendai virus are used as well ( Figure 3) 32,41, [45][46][47][48][49] . The majority of these vectors are delivered intramuscularly, enter the vaccinees' cells and then express the spike protein to which the host immune system responds.…”

Section: Replication Inactive Vectorsmentioning

confidence: 99%

SARS-CoV-2 vaccines in development

Krammer

2020

Nature

1,867

1,781

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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Section: Replication Inactive Vectorsmentioning

confidence: 99%

SARS-CoV-2 vaccines in development

Krammer

2020

Nature

1,867

1,781

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“…Indeed to address the urgent need for a safe and e cacious vaccine against the SARS-CoV-2 several vibrant initiatives have been started as never before. For example, vaccine manufacturing front-runner come-up with mRNA vaccines [44], viral vector vaccine [45], classical attenuated vaccine etc. [46].…”

Section: Resultsmentioning

confidence: 99%

A novel peptide analogue of spike glycoprotein shows antiviral properties against SARS-CoV-2: An in silico approach through molecular docking, molecular dynamics simulation and MM-PB/GBSA calculations

Dutta

Elmezayen

Al-Obaidi

et al. 2020

Preprint

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At the very beginning of the new decade, the COVID-19 pandemic has badly hit modern human societies. SARS-CoV-2, the causative agent of COVID-19 carries dozens of new mutations in its genome. Herein, we made an effort to find new antiviral peptides (AVPs) against SARS-CoV-2. Gladly, with the help of Machine Learning algorithms, and Supported Vector Machine, we have invented three new AVPs against the SARS-CoV-2. Antiviral peptides viz., Seq12, Seq12m, and Seq13m can block the receptor binding domain (RBD) of the SARS-CoV-2, necessary for communication with the angiotensin-converting enzyme 2 (ACE2). In addition, these AVPs retain their antiviral properties, even after the insertion of dozens of new mutations (Rosetta, and FoldX based) in the RBD. Further, Seq12, and Seq12m showed negligible cytotoxicity. Besides, the binding free energy calculated using MM-PB/GBSA method is also in agreement with the molecular docking studies performed using HADDOCK. Furthermore, the molecular interactions between AVPs and the viral membrane protein (M) also showed a thermodynamically favorable interaction, suggesting it could eventually inhibit the viral re-packaging process. In conclusion, this study suggests AVPs viz., Seq12, Seq12m, and Seq13m embrace importance as a potential anti-SARS-CoV-2 therapeutic. These AVPs could also aid virus diagnostic tools in the future.

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“…In addition, specific IFN-γ secretion T cell response was prolonged at high level after boosting vaccination. Two recent publications compared prime only with a single-dose of ChAdOx1 nCoV-19 and homologous boost with a second dose of ChAdOx1 nCoV-19 vaccine in mice and pigs, and human clinical trials, showed that boost vaccination significantly increased and prolonged the level of binding or neutralizing antibody response to SARS-CoV-2 ( 11, 20 ). By boosting with Ad5-S vaccine the Ad26-S vaccine primed immunization, a higher level of immunity was observed in humans as reported in a recent Russian study ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…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 ).…”

Section: Introductionmentioning

confidence: 99%

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

Luo

Zhang

Liu

et al. 2020

Preprint

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COVID-19 vaccines are being developed urgently worldwide, among which single-shot adenovirus vectored vaccines represent a major approach. Here, we constructed two novel adenovirus vectored COVID-19 vaccine candidates on simian adenovirus serotype 23 (Sad23L) and human adenovirus serotype 49 vectors (Ad49L) carrying the full-length gene of SARS-CoV-2 spike protein (S), designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. The immunogenicity elicited by these two vaccine strains was individually evaluated in mice. Specific humoral and cellular immune responses were proportionally observed in a dose-dependent manner, and stronger response was obtained by boosting. Furthermore, five rhesus macaques were intramuscularly injected with a dose of 5×109 PFU Sad23L-nCoV-S vaccine for prime vaccination, followed by boosting with 5×109 PFU of Ad49L-nCoV-S vaccine at 4-week interval. Three macaques were injected with Sad23L-GFP and Ad49L-GFP vectorial viruses as negative controls. Both mice and macaques tolerated well the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost vaccination regimen induced high titers of 103.16 S-binding antibody (S-BAb), 102.75 cell receptor binding domain (RBD)-BAb and 102.38 neutralizing antibody (NAb) to pseudovirus a week after boosting injection, followed by sustained high levels over 10 weeks of observation. Robust IFN-γ secreting T-cell response (712.6 SFCs/106 cells), IL-2 secreting T-cell response (334 SFCs/106 cells) and intracellular IFN-γ expressing CD4+/CD8+ T cell response (0.39%/0.55%) to S peptides were detected in the vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

show abstract

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Cited by 127 publications

References 25 publications

SARS-CoV-2 vaccines in development

SARS-CoV-2 vaccines in development

A novel peptide analogue of spike glycoprotein shows antiviral properties against SARS-CoV-2: An in silico approach through molecular docking, molecular dynamics simulation and MM-PB/GBSA calculations

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

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