A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate

Sánchez-Felipe, Lorena; Vercruysse, Thomas; Sharma, Sapna; Ma, Ji; Lemmens, Viktor; Looveren, Dominique Van; Javarappa, Mahadesh Prasad Arkalagud; Boudewijns, Robbert; Malengier‐Devlies, Bert; Liesenborghs, Laurens; Kaptein, Suzanne; Keyzer, Carolien De; Bervoets, Lindsey; Debaveye, Sarah; Rasulova, Madina; Seldeslachts, Laura; Li, Li Hsin; Jansen, S.L.; Yakass, Michael Bright; Verstrepen, Babs E.; Böszörményi, Kinga P.; Kiemenyi-Kayere, Gwendoline; Driel, Nikki van; Quaye, Osbourne; Zhang, Xin; Horst, Sebastiaan ter; Mishra, Niraj; Deboutte, Ward; Matthijnssens, Jelle; Coelmont, Lotte; Vandermeulen, Corinne; Heylen, Elisabeth; Vergote, Valentijn; Schols, Dominique; Wang, Zhongde; Bogers, Willy; Kuiken, Thijs; Verschoor, Ernst J.; Cawthorne, Christopher; Laere, Koen Van; Opdenakker, Ghislain; Velde, Greetje Vande; Weynand, Birgit; Teuwen, Dirk E.; Matthys, Patrick; Neyts, Johan; Thibaut, Hendrik Jan; Dallmeier, Kai

doi:10.1038/s41586-020-3035-9

Cited by 173 publications

(306 citation statements)

References 78 publications

Supporting

Mentioning

279

Contrasting

Order By: Relevance

“…Housing and experimental infections of hamsters have been described 15–17 and conducted under supervision of the ethical committee of KU Leuven (license P015-2020). In brief, 6 to 8 weeks old female Syrian hamster ( Mesocricetus auratus ) were sourced from Janvier Laboratories and kept per two in individually ventilated isolator cages.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Abdelnabi

Boudewijns

Foo

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Within one year after its emergence, more than 108 million people contracted SARS-CoV-2 and almost 2.4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1), variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics and new spikes in excess mortality. We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 lineages in Syrian golden hamsters to assess their relative infectivity and pathogenicity in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020. A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected. Overall, we established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Here, we investigate infection of Syrian hamsters with prototypic VoC, namely local Belgian low-passage isolates from both B.1.1.7 and B.1.351 lineages (Fig 1A, B). 15–17…”

Section: Introductionmentioning

confidence: 99%

Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Abdelnabi

Boudewijns

Foo

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the impact of prior infection on blocking SARS-CoV-2 transmission is not clear. As a small animal model, golden hamsters have been used for studying pathogenesis 18,19 , transmission ability 20 of SARS-CoV-2 and for evaluating potential vaccines 21,22 and antiviral drugs 23 . Here, we evaluated the impact of prior infection on protection and transmission of SARS-CoV-2 in golden hamsters.…”

Section: The Main Textmentioning

confidence: 99%

Impact of Prior Infection on Protection and Transmission of SARS-CoV-2 in Golden Hamsters

Zhang

Guo²,

Li³

et al. 2021

Preprint

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 100 million confirmed human infections, and 2 million more deaths globally since its emergence in the end of 2019. Several studies have shown that prior infection provided protective immunity against SARS-CoV-2 in non-human primate models. However, the effect of prior infection on blocking SARS-CoV-2 transmission is not clear. Here, we evaluated the impact of prior infection on protection and transmission of the SARS-CoV-2 virus in golden hamsters. Our results showed that prior infection provided protective immunity against SARS-CoV-2 re-challenge, but it was not sterizing immunity. The transmission experiment results showed that SARS-CoV-2 was efficiently transmitted from naive hamsters to prior infected hamsters by direct contact and airborne route, but not by indirect contact. Further, the virus was efficiently transmitted from prior infected hamsters to naive hamsters by direct contact, but not by airborne route and indirect contact. Surprisingly, the virus can be transmitted between prior infected hamsters by direct contact during a short period of early infection. Taken together, our study demonstrated that prior infected hamsters with good immunity can still be naturally re-infected, and the virus can be transmitted between prior infected hamsters and the naive through different transmission routes, implying the potential possibility of human re-infection and the risk of virus transmission between prior infected population and the healthy. Our study will help to calculate the herd immunity threshold more accurately, make more reasonable public health decisions, formulate an optimized population vaccination program, as well as aid the implementation of appropriate public health and social measures to control COVID-19.

show abstract

“…Using S1 rather than the full spike protein as the immunogen ensures the immune responses against the important neutralizing epitopes identified in human convalescent patients recognizing the RBD, NTD S1, and quaternary epitope that bridges the two RBDs (37). Our use of the S1 in CORAVAX might explain the higher VNA titers in the Syrian hamsters compared to other Covid-19 vaccines utilizing the full spike as the antigen in yellow fever and Ad26 vectors as well as in a DNA vaccine platform (38)(39)(40). CORAVAX induced high SARS CoV-2 S1 and RBD specific antibody and neutralizing titers on day 26 post the prime vaccination.…”

Section: Discussionmentioning

confidence: 97%

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

Kurup

Malherbe

Wirblich

et al. 2021

Preprint

View full text Add to dashboard Cite

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

show abstract

A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate

Cited by 173 publications

References 78 publications

Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Comparative infectivity and pathogenesis of emerging SARS-CoV-2 variants in Syrian hamsters

Impact of Prior Infection on Protection and Transmission of SARS-CoV-2 in Golden Hamsters

Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

Contact Info

Product

Resources

About