Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

ABSTRACT

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Related collections

Most cited references 55

Record: found
Abstract: found
Article: not found

Virological assessment of hospitalized patients with COVID-2019

Roman Wölfel, Victor M Corman, Wolfgang Guggemos … (2020)

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

0 comments Cited 3449 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Structural basis of receptor recognition by SARS-CoV-2

Jian Ku Shang, Gang Ye, Ke Chuang Shi … (2020)

Summary A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans 1,2 . A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2) 3,4 . Here we determined the crystal structure of SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of hACE2. Compared with SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we showed that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.

0 comments Cited 1871 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

SARS-CoV-2 variants, spike mutations and immune escape

William T. Harvey, Alessandro M. Carabelli, Ben Jackson … (2021)

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

0 comments Cited 1512 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Emerg Microbes Infect

Journal ID (iso-abbrev): Emerg Microbes Infect

Title: Emerging Microbes & Infections

Publisher: Taylor & Francis

ISSN (Electronic): 2222-1751

Publication date (Electronic, pub): 12 August 2021

Publication date (Electronic, collection): 2021

Volume: 10

Issue: 1

Pages: 1574-1588

Affiliations

[a ]Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Tropical Medicine and Laboratory Medicine, The First Afﬁliated Hospital, Hainan Medical University , Haikou, People’s Republic of China

[b ]Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing, People’s Republic of China

[c ]Savaid Medical School, University of Chinese Academy of Sciences , Beijing, People’s Republic of China

[d ]Chengdu Kanghua Biological Products Co., Ltd , Chengdu, People’s Republic of China

[e ]Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) , Beijing, People’s Republic of China

[f ]Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University , Nanning, People’s Republic of China

[g ]School of Public Health, Cheeloo College of Medicine, Shandong University , Jinan, People’s Republic of China

[h ]CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing, People’s Republic of China

[i ]CAS Center for Inﬂuenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences , Beijing, People’s Republic of China

[j ]National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing, People’s Republic of China

[k ]Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, People’s Republic of China

Author notes

[CONTACT ] Lianpan Dai dailp@ 123456im.ac.cn

George F. Gao gaof@ 123456im.ac.cn

Qianfeng Xia xiaqianfeng@ 123456hainmc.edu.cn

Wenli Hou hwl@ 123456kangh.com

Qinghan Wang wqh@ 123456kangh.com

[*]

These authors contributed equally to this work.

Supplemental data for this article can be accessed at https://doi.org/10.1080/22221751.2021.1959270

Author information

Kun Xu https://orcid.org/0000-0002-9762-5001

Yuhai Bi https://orcid.org/0000-0002-5595-363X

George F. Gao https://orcid.org/0000-0002-3869-615X

Lianpan Dai https://orcid.org/0000-0001-8352-1327

Article

Publisher ID: 1959270

DOI: 10.1080/22221751.2021.1959270

PMC ID: 8366625

PubMed ID: 34289779

SO-VID: ad8fd8cd-5f5e-48a3-96ae-6f7960cbfbbd

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19

Read this article at

ABSTRACT

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 55

Virological assessment of hospitalized patients with COVID-2019

Structural basis of receptor recognition by SARS-CoV-2

SARS-CoV-2 variants, spike mutations and immune escape

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 139

Cited by 13

Most referenced authors 4,413