A rapid strategy for constructing novel simian adenovirus vectors with high viral titer and expressing highly antigenic proteins applicable for vaccine development

Luo, Songyuan; Zhang, Panli; Ma, Xiaorui; Wang, Qi; Lu, Jinhui; Liu, Bochao; Zhao, Wei; Allain, Jean‐Pierre; Li, Chengyao; Li, Tingting

doi:10.1016/j.virusres.2019.05.008

Cited by 19 publications

(27 citation statements)

References 37 publications

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“…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 ).…”

Section: Discussionmentioning

confidence: 94%

“…The intact S glycoprotein rather than the shorter S or RBD proteins was shown to be the most effective antigen eliciting protective immunity against SARS-CoV-2 infection in DNA vaccines and Ad26 vectored vaccines ( 12,13,26 ). 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.…”

Section: Discussionmentioning

confidence: 99%

“…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 ). Compared with homologous boosting of ChAdOx1 nCoV-19 or boosting of Ad5-S vaccines ( 11, 21 ), heterologous prime-boost vaccinations with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines have the advantage of avoiding vector’s immunity interfering with prime vaccination or enhancing pre-existing Ad5 immunity ( 22–25 ).…”

Section: Discussionmentioning

confidence: 99%

“…According to the description of Sad23L vector (SAdV23, GenBank: AY530877.1) ( 22, 23 ), the replication defective adenoviral vector Ad49L was constructed by deleting the E1 and E3 regions of the full-length human adenovirus serotype 49 genome (HAdV49, GenBank: DQ393829.1). The E4 region open reading frame 6 (orf6) was replaced by the corresponding element of human adenovirus type 5 (Ad5) in order to improve virus propagating efficiency.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, two novel simian adenovirus type 23 (SAdV23) and human adenovirus type 49 (HAdV49) derived vectors (Sad23L and Ad49L) were used for developing the COVID-19 vaccines carrying the full-length S gene of SARS-CoV-2 ( 22, 23 ) designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. These two adenovirus vectored COVID-19 vaccines presented high infectious titers and low frequencies of pre-existing immunity in humans.…”

Section: Introductionmentioning

confidence: 99%

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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.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Luo

Zhang

Liu

et al. 2020

Preprint

Self Cite

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Recovery and Genetic Characterization of a West Nile Virus Isolate from China

Guo

Wang²,

et al. 2020

Virol. Sin.

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A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

et al. 2021

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SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines. However, the thermal instability and pre-existing immunity have limited its wide applications. To circumvent these obstacles, we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine (Sad23L-nCoV-S-CaP) by generating a calcium phosphate mineral exterior (CaP) based on Sad23L vector carrying the full-length gene of SARS-CoV-2 spike protein (S) under physiological condition. This Sad23L-nCoV-S-CaP vaccine was examined for its characteristics of structure, thermostability, immunogenicity and avoiding the problem of preexisting immunity. In thermostability test, Sad23L-nCoV-S-CaP could be stored at 4 °C for over 45 days, 26 °C for more than 8 days and 37 °C for approximately 2 days. Furthermore, Sad23L-nCoV-S-CaP induced higher level of S-specific antibody and T cell responses, and was not affected by the pre-existing anti-Sad23L immunity, suggesting it could be used as boosting immunization on Sad23L-nCoV-S priming vaccination. The boosting with Sad23L-nCoV-S-CaP vaccine induced high titers of 10 5.01 anti-S1, 10 4.77 anti-S2 binding antibody, 10 3.04 pseudovirus neutralizing antibody (IC 50 ), and robust T-cell response of IFN-γ (1466.16 SFCs/10 6 cells) to S peptides, respectively. In summary, the self-biomineralization of the COVID-19 vaccine Sad23L-nCoV-S-CaP improved vaccine efficacy, which could be used in prime-boost regimen for prevention of SARS-CoV-2 infection in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00434-3.

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A rapid strategy for constructing novel simian adenovirus vectors with high viral titer and expressing highly antigenic proteins applicable for vaccine development

Cited by 19 publications

References 37 publications

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

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

Recovery and Genetic Characterization of a West Nile Virus Isolate from China

A Self-Biomineralized Novel Adenovirus Vectored COVID-19 Vaccine for Boosting Immunization of Mice

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