doi: 10.1038/s41467-020-17972-1.
A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge
Shipo Wu # 1, Gongxun Zhong # 2, Jun Zhang # 1, Lei Shuai # 2, Zhe Zhang 1, Zhiyuan Wen 2, Busen Wang 1, Zhenghao Zhao 1, Xiaohong Song 1, Yi Chen 1, Renqiang Liu 2, Ling Fu 1, Jinlong Zhang 1, Qiang Guo 1, Chong Wang 2, Yilong Yang 1, Ting Fang 1, Peng Lv 1, Jinliang Wang 2, Junjie Xu 1, Jianmin Li 1, Changming Yu 1, Lihua Hou 3, Zhigao Bu 4, Wei Chen 5
Affiliations
- PMID:32796842
- PMCID: PMC7427994
- DOI: 10.1038/s41467-020-17972-1
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A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge
Shipo Wu et al. Nat Commun..
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Abstract
The unprecedented coronavirus disease 2019 (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective vaccine to control this severe infectious disease. Here, we find that a single vaccination with a replication-defective human type 5 adenovirus encoding the SARS-CoV-2 spike protein (Ad5-nCoV) protect mice completely against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. Additionally, a single vaccination with Ad5-nCoV protects ferrets from wild-type SARS-CoV-2 infection in the upper respiratory tract. This study suggests that the mucosal vaccination may provide a desirable protective efficacy and this delivery mode is worth further investigation in human clinical trials.
Conflict of interest statement
The authors declare no competing interests.
Figures
a Schematic of SARS-CoV-2 S immunogens.b Western blot of transgene expression from (1) Soriginal, (2) SPtPA add Smature, (3) SPoriginal add Soptimized, (4) SPtPA add Soptimized, and (5) an empty plasmid transfected in HEK293 cells. BALB/c mice (n = 10 per group) received a single immunization with different doses of Ad5-nCoV or Ad5 vector by the IM or IN route.c–h, Humoral immune responses were assessed at weeks 0, 2, 4, 6 and 8 following vaccination by S-specific ELISAc,f, SARS-CoV-2 NAb titration (MN50)d,g and SARS-CoV-2 PNAb titratione,h withn = 10 biologically independent animals per group. Data represent the individual titre of each animal and the connecting lines reflect the geometric means of the titres.i,j, Cellular immune responses were assessed at day 14 following vaccination in the 5 × 108 VP dose groups by intracellular cytokine staining assays withn = 10 biologically independent animals per group. Data are presented as mean ± s.e.m. Statistical significance was determined by Kruskal–Wallis ANOVA with Dunn’s multiple comparisons tests. S = spike protein, SP = signal peptide, tPA = tissue plasminogen activator. Dotted line = the limit of detection. Source data are provided as a Source Data file.
BALB/c mice (n = 10 biologically independent animals per group) received a single immunization with different doses of Ad5-nCoV or Ad5 vector by the IM or IN route, and seven of ten mice were challenged at week 10 with 103.6 PFU of mouse-adapted SARS-CoV-2 virus HRB26M in a volume of 50 μL by the IN route. Tissue live virus numbersa and tissue viral loadsb were detected at 3 dpi (n = 4 biologically independent animals per group) and 5 dpi (n = 3 biologically independent animals per group) in the lungs and turbinates, respectively. Black bars reflect geometric means; 3 dpi = red circles; 5 dpi = blue squares; dotted line = the limit of detection. Source data are provided as a Source Data file.
Ferrets (n = 6 biologically independent animals per group) received a single immunization by the IM route or two simultaneous doses by the IN and oral routes with 5 × 1010 VP per dose of Ad5-nCoV or received a sham vaccine. Humoral immune responses were assessed at week 4 following vaccination by S-specific ELISA (a) and NAb titration (PRNT90) (b).c Cellular immune response was assessed by IFNγ ELISpot assays. Live virus numbers (d) and viral load (e) of SARS-CoV-2 in nasal washes obtained from ferrets after challenge. Bar at the geometric mean, and connecting lines reflect geometric means; statistical significance was determined by Kruskal–Wallis ANOVA with Dunn’s multiple comparisons tests; IN and oral inoculation animals = red circles; IM injection animals = blue squares; control animals = brown triangles; dotted line = the limit of detection. Source data are provided as a Source Data file.
References
- WHO. Draft landscape of COVID-19 candidate vaccines–15 July 2020.https://www.who.int/publications/m/item/draft-landscape-of-covid-19-cand.... Accessed 19 July 2020.
- van Doremalen, N. et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.Nature, 10.1038/s41586-020-2608-y (2020). - PubMed
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