A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge

Wu, Shipo; Zhong, Gongxun; Zhang, Jun; Shuai, Lei; Zhang, Zhe; Wen, Zhiyuan; Wang, Busen; Zhao, Zeyao; Song, Xiaohong; Chen, Yi; Liu, Renqiang; Fu, Ling; Zhang, Jinlong; Guo, Qiang; Wang, Chong; Yang, Yating; Fang, Ting; Lv, Ping; Wang, Jinliang; Xu, Junjie; Li, Jianmin; Yu, Changming; Hou, Lihua; Bu, Zhigao; Chen, Wei

doi:10.1038/s41467-020-17972-1

Cited by 244 publications

(256 citation statements)

References 21 publications

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“…While it fortunately appears that SARS-CoV-2 and many of the vaccine candidates in clinical trials can readily stimulate immune responses, (see e.g. (Corbett et al, 2020; Feng et al, 2020; Mulligan et al, 2020; Suthar et al, 2020; Wu, S. et al, 2020)), stringent assessment of antigens and careful selection of delivery vehicles are still necessary before it comes to mass vaccination. Careful selection of antigens is critical for avoiding unfavorable immune reactions and disease enhancement, as in the past experienced with RSV, measles and dengue vaccines (for reviews see (Lee et al, 2020; Ruckwardt et al, 2019)).…”

Section: Discussionmentioning

confidence: 99%

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Hennrich

Banda

Oberhuber

et al. 2020

Preprint

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The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which may cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients. Boost immunization with the identical replicon further enhanced neutralizing activity. These results demonstrate that rhabdovirus minispike replicons represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.

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Section: Discussionmentioning

confidence: 99%

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Hennrich

Banda

Oberhuber

et al. 2020

Preprint

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“…At present, more than one hundred of vaccine development projects being carried out globally ranged from viral vector-based vaccines, mRNA and DNA vaccines, subunit vaccines, nano-particle-based vaccines, to inactivated-whole virus vaccines [5][6][7][8] . Some vaccine candidates such as inactivated vaccine can inhibit virus replication and protect against upper respiratory tract disease, and other vaccine candidates such as Ad5-nCoV encoding the full spike of SARS-CoV-2 demonstrate good characteristics in both safety and immunogenicity [5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

“…None of the 18 linear B-cell epitopes were found toxic.Four linear B-cell epitopes specifically binding with serum antibodies from the animals inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19Animal models are necessary to demonstrate efficacy and safety in the development of vaccines against SARS-CoV-2 infection58,59 . BALB/c mice is a good animal model for investigating SARS-CoV-2 infection in both upper and lower respiratory tracts5 . Monkey, phylogenetically close to humans, has been used to test whether seroconversion provides protective immunity against SARS-CoV-258 .…”

mentioning

confidence: 99%

“…Safe and effective vaccines are urgently needed to be developed and deployed in a rapid but highly reliable manner. More than one hundred projects are being executed in the WHO draft landscape of COVID-19 candidate vaccines including a variety of vaccine types such as viral vector-based vaccines, mRNA and DNA vaccines, subunit vaccines, nanoparticlebased vaccines, to inactivated-whole virus vaccines[5][6][7][8][9] . However, even for vaccines in clinical trial phase III,some mild side effects are still observed and sporadically reported.…”

mentioning

confidence: 99%

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Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Zhao

Yang

et al. 2020

Preprint

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SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with serum antibodies from horse, mouse, and monkey inoculated with different SARS-CoV-2 vaccine candidates or a patient recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

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“…6 7 Adenoviral vectors are currently strong candidate vaccines against the recently emerged SARS-CoV-2 causing the pandemic COVID-19. [8][9][10][11] Adenoviruses are also frequently used as platforms for gene therapy, oncolytic therapy and vaccines in cancer treatment. 12 Regarding the cancer vaccine platform, several adenoviral vectors are currently in clinical trials for (preventive) treatment against prostate cancer, pancreatic cancer and human papilloma virus (HPV)-associated cancer.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

Gracht

Schoonderwoerd

Duikeren

et al. 2020

J Immunother Cancer

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BackgroundAdenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8+ T cells elicited upon immunization with adenoviral vectors.MethodsAdenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (107, 108 or 109 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated.ResultsThe adenoviral vaccines elicited inflationary E7-specific memory CD8+ T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8+ T cells in the circulation related to the development of E7-specific CD8+ tissue-resident memory T (TRM) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8+ T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8+ TRM cells. Moreover, the formation of CD8+ TRM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization.ConclusionsTogether, these data show that adenoviral vector-induced CD8+ T cell inflation promotes protective TRM cell populations, and this can be enhanced by targeting CTLA-4.

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A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge

Cited by 244 publications

References 21 publications

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

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