Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals

Ye, Zi‐Wei; Ong, Chon Phin; Tang, Kaiming; Fan, Yilan; Luo, Cheng; Zhou, Run; Luo, Peng; Cao, Yun; Gray, Victor Sebastien; Wang, Pui; Chu, Hin; Chan, Jasper Fuk‐Woo; To, Kelvin Kai-Wang; Chen, Honglin; Chen, Zhiwei; Yuen, Kwok‐Yung; Ling, Guang Sheng; Yuan, Shuofeng; Jin, Dong Yan

doi:10.1038/s41423-022-00855-4

Cited by 30 publications

(33 citation statements)

References 70 publications

(85 reference statements)

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“…However, for optimal protection in the upper respiratory tract, mucosal immunity is required [19]. In this regard, nasal administration of live attenuated vaccines and influenza virus-based vaccines expressing SARS-CoV-2 spike protein as either primary or booster immunization might provide the desired effect [47][48][49]. It will be of interest to see whether these vaccines might be good inducers of mucosal immunity and secretory IgA in the upper respiratory tract.…”

Section: Discussionmentioning

confidence: 99%

Cross-variant protection against SARS-CoV-2 infection in hamsters immunized with monovalent and bivalent inactivated vaccines

Ye¹,

Fan²,

Tang³

et al. 2022

Int. J. Biol. Sci.

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Rapid development and successful use of vaccines against SARS-CoV-2 might hold the key to curb the ongoing pandemic of COVID-19. Emergence of vaccine-evasive SARS-CoV-2 variants of concern (VOCs) has posed a new challenge to vaccine design and development. One urgent need is to determine what types of variant-specific and bivalent vaccines should be developed. Here, we compared homotypic and heterotypic protection against SARS-CoV-2 infection of hamsters with monovalent and bivalent whole-virion inactivated vaccines derived from representative VOCs. In addition to the ancestral SARS-CoV-2 Wuhan strain, Delta (B.1.617.2; δ) and Theta (P.3; θ) variants were used in vaccine preparation. Additional VOCs including Omicron (B.1.1.529) and Alpha (B.1.1.7) variants were employed in the challenge experiment. Consistent with previous findings, Omicron variant exhibited the highest degree of immune evasion, rendering all different forms of inactivated vaccines substantially less efficacious. Notably, monovalent and bivalent Delta variant-specific inactivated vaccines provided optimal protection against challenge with Delta variant. Yet, some cross-variant protection against Omicron and Alpha variants was seen with all monovalent and bivalent inactivated vaccines tested. Taken together, our findings support the notion that an optimal next-generation inactivated vaccine against SARS-CoV-2 should contain the predominant VOC in circulation. Further investigations are underway to test whether a bivalent vaccine for Delta and Omicron variants can serve this purpose.

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Section: Discussionmentioning

confidence: 99%

Cross-variant protection against SARS-CoV-2 infection in hamsters immunized with monovalent and bivalent inactivated vaccines

Ye¹,

Fan²,

Tang³

et al. 2022

Int. J. Biol. Sci.

Self Cite

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“…In a prime-boost context, double sCPD9 immunisation was superior to mRNA-sCPD9 vaccination, followed by double mRNA vaccination and double adenovirus vaccination [58]. On the one hand, sCPD9-vaccinated mice displayed a considerable decrease in the activation of pro-inflammatory gene expression programmes, which contributed significantly to COVID-19 pathogenesis [5]. This was especially true for cells of the innate immune system, such as monocytes and macrophages, demonstrating robust proinflammatory transcriptional responses during SARS-CoV-2 absorption [16].…”

Section: A Live Attenuated Vaccination Confers Superior Mucosal and S...mentioning

confidence: 99%

“…Mucosal IgA aids the local immune response in several ways, including preventing mucins from leaking, viruses from entering, merging with endosomal membranes within cells, and viruses from escaping host cells [7,56]. Vaccinated animals were more protected than others against viral multiplication, tissue damage, and lung inflammation [5]. These discoveries are likely the consequence of the distinctive properties of live attenuated vaccines, including delivery by the natural route of infection, presentation of the whole antigenic repertoire of the virus, and replication emulating the target pathogen [19].…”

Section: A Live Attenuated Vaccination Confers Superior Mucosal and S...mentioning

confidence: 99%

“…The destructive COVID-19 pandemic caused by SARS-CoV-2 has set a new phase in which breakthrough infections, specifically those caused by the highly transmittable Omicron and Delta variants, are widespread to a higher degree in vaccines immunized with mRNA, adenoviral vector, protein subunit or inactivated vaccines [3,4]. In regards to the waning of protective immunity in vaccines over time and the exigency of vaccine-escaped SARS-CoV-2 variants, another injection of booster is suggested, and the development of variant-targeted vaccines is ongoing [5]. The levels of neutralizing antibodies (NAbs) that aim the viral spike (S) protein, especially the receptor-binding domain (RBD), relate superbly with protective immunity against detectable and symptomatic SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

“…Evidently, the probability of establishing sterilizing immunity would be substantially gone up when a live attenuated vaccine is applied as a injection booster in people who have been naturally infected or immunized with an mRNA vaccine or another type of vaccine [10,15]. However, live attenuated vaccines are comprehended to elicit a much wider range of humoral and cellular immune responses that are cross-reactive and cross-protective [5,16]. They might contribute considerably to the SARS-CoV-2 control in the next station of the pandemic [10].…”

Section: Introductionmentioning

confidence: 99%

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The Advantage Efficacy of Intranasal Live-Attenuated Vaccine Against SARS-CoV-2

Sae-ngow

2022

Int J Sci Healthcare Res

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Coronavirus disease 2019 (COVID-19) has ushered in a new era of breakthrough infections. The SARS-CoV-2 virus, which causes COVID-19, emerged in late 2019 in a seafood market in Wuhan, China, and was linked to pneumonia-associated sickness, which can culminate in respiratory failure. COVID-19 can potentially cause cardiovascular and gastrointestinal diseases and indicate an inflammatory condition. Regarding the diminishing protective immunity of vaccinations over time and the urgency of vaccine-evading SARS-CoV-2 variations, it is recommended that a booster injection be administered, and the research of variant-specific vaccines is continuing. As a result of the COVID-19 pandemic, vaccine development became a focal point of global research. However, vaccine development necessitates considerable time. Between preclinical research and the final vaccine's commercialisation, years or more than a decade are often required. Several options for SARS-CoV-2 vaccines have begun clinical trials globally after months of research and development. As stipulated by the WHO, vaccine development must involve preclinical research, clinical application, clinical trial agency application, registered clinical trial, phase I clinical trial, phase II clinical trial, phase III clinical trial, marketing, and manufacture of the vaccine. It is essential to create a balanced list of the benefits and drawbacks of deploying LAVs so that a well-informed choice can be made on which LAVs may be dispatched promptly to prevent and manage unanticipated pandemic breakouts. Keywords: Intranasal live-attenuated vaccine, Covid-19 vaccine, SAR-CoV-2

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Production of single‐cycle infectious SARS‐CoV‐2 through a trans‐complemented replicon

Cheung

Lui

et al. 2022

Journal of Medical Virology

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Single‐cycle infectious virus can elicit close‐to‐natural immune response and memory. One approach to generate single‐cycle severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is through deletion of structural genes such as spike (S) and nucleocapsid (N). Transcomplementation of the resulting ΔS or ΔN virus through enforced expression of S or N protein in the cells gives rise to a live but unproductive virus. In this study, ΔS and ΔN BAC clones were constructed and their live virions were rescued by transient expression of S and N proteins from the ancestral and the Omicron strains. ΔS and ΔN virions were visualized by transmission electron microscopy. Virion production of ΔS was more efficient than that of ΔN. The coated S protein from ΔS was delivered to infected cells in which the expression of N protein was also robust. In contrast, expression of neither S nor N was detected in ΔN‐infected cells. ΔS underwent viral RNA replication, induced type I interferon (IFN) response, but did not form plaques. Despite RNA replication in cells, ΔS infection did not produce viral progeny in culture supernatant. Interestingly, viral RNA replication was not further enhanced upon overexpression of S protein. Taken together, our work provides a versatile platform for development of single‐cycle vaccines for SARS‐CoV‐2.

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Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals

Cited by 30 publications

References 70 publications

Cross-variant protection against SARS-CoV-2 infection in hamsters immunized with monovalent and bivalent inactivated vaccines

Cross-variant protection against SARS-CoV-2 infection in hamsters immunized with monovalent and bivalent inactivated vaccines

The Advantage Efficacy of Intranasal Live-Attenuated Vaccine Against SARS-CoV-2

Production of single‐cycle infectious SARS‐CoV‐2 through a trans‐complemented replicon

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