Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

Kulkarni, Rakesh; Chen, Wen-Ching; Lee, Ying; Kao, Chi‐Fei; Hu, Shiu‐Lok; Ma, Hsiu-Hua; Jan, Jia-Tsrong; Liao, Chun-Che; Liang, Jian-Jong; Ko, Hui-Ying; Sun, Cheng‐Pu; Lin, Yin-Shoiou; Wang, Yu-Chiuan; Wei, Sung-Chan; Ma, Che; Chao, Yu-Chan; Chou, Yu‐Chi; Chang, Wen

doi:10.1101/2021.08.03.454910

Cited by 3 publications

(1 citation statement)

References 140 publications

(190 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mouse kidney histology was assessed as described previously (Kulkarni et al , 2021) with some modifications. The kidneys of WT and cKO mice were removed on 7 d.p.i and fixed in 4% paraformaldehyde for 2 days at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function againstCandida albicans

Kulkarni

Kasani

Tsai

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

FAM21 (family with sequence similarity 21) is a component of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) protein complex that mediates actin polymerization at endosomal membranes to facilitate sorting of cargo-containing vesicles out of endosomes. To study the function of FAM21 in vivo, we generated conditional knockout (cKO) mice in the C57BL/6 background in which FAM21 was specifically knocked out of CD11c-positive dendritic cells. Bone marrow-derived dendritic cells (BMDC) from those mice displayed enlarged early endosomes, and altered cell migration and morphology relative to wildtype (WT) cells. FAM21-cKO cells were less competent in phagocytosis and antigen processing in vitro, though antigen presentation was not affected. More importantly, we identified the TLR2/CLEC4E signaling pathway as being downregulated in FAM21-cKO BMDCs when challenged with its specific ligand Candida albicans. Moreover, FAM21-cKO mice were more susceptible to C. albicans infection than WT mice. Reconstitution of WT BMDCs in FAM21-cKO mice rescued them from lethal C. albicans infection. Thus, our study highlights the importance of FAM21 in a host immune response against a significant pathogen.

show abstract

Section: Methodsmentioning

confidence: 99%

FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function againstCandida albicans

Kulkarni

Kasani

Tsai

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

Meekins

Gaudreault

Richt

2021

Viruses

View full text Add to dashboard Cite

SARS-CoV-2 is the etiological agent responsible for the ongoing COVID-19 pandemic, which continues to spread with devastating effects on global health and socioeconomics. The susceptibility of domestic and wild animal species to infection is a critical facet of SARS-CoV-2 ecology, since reverse zoonotic spillover events resulting in SARS-CoV-2 outbreaks in animal populations could result in the establishment of new virus reservoirs. Adaptive mutations in the virus to new animal species could also complicate ongoing mitigation strategies to combat SARS-CoV-2. In addition, animal species susceptible to SARS-CoV-2 infection are essential as standardized preclinical models for the development and efficacy testing of vaccines and therapeutics. In this review, we summarize the current findings regarding the susceptibility of different domestic and wild animal species to experimental SARS-CoV-2 infection and provide detailed descriptions of the clinical disease and transmissibility in these animals. In addition, we outline the documented natural infections in animals that have occurred at the human–animal interface. A comprehensive understanding of animal susceptibility to SARS-CoV-2 is crucial to inform public health, veterinary, and agricultural systems, and to guide environmental policies.

show abstract

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

et al. 2023

View full text Add to dashboard Cite

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and was correctly processed and transported to the cell surface, where it efficiently produced cell–cell fusion. Version Spf, however, was not proteolytically processed, and despite being transported to the plasma membrane, it failed to induce cell–cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin-converting enzyme 2 (K18-hACE2) in mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the level of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine.

show abstract

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

Cited by 3 publications

References 140 publications

FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function againstCandida albicans

FAM21 is critical for TLR2-CLEC4E-mediated dendritic cell function againstCandida albicans

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

Contact Info

Product

Resources

About