SARS-CoV-2 immunity in animal models

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication through competitively blocking the virus entry

Since the outbreak of coronavirus disease 2019(COVID-19),it has become a global pandemic.The spike(S)protein of etiologic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specifically recognizes human angiotensin-converting enzyme 2(hACE2)as its receptor,which is recently identified as an interferon(IFN)-stimulated gene.Here,we find that hACE2 exists on the surface of exosomes released by different cell types,and the expression of exosomal hACE2 is increased by IFNα/β treatment.In particular,exosomal hACE2 can specifically block the cell entry of SARS-CoV-2,subsequently inhibit the replication of SARS-CoV-2 in vitro and ex vivo.Our findings have indicated that IFN is able to upregulate a viral receptor on the exosomes which competitively block the virus entry,exhibiting a potential antiviral strategy.

Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles

To the Editor:Coronavirus disease 2019(COVID-19)has become a worldwide public health emergency,threatening public health and global stability[1].The development of a safe and effective vaccine is urgently needed to control the pandemic.Generally,nanoparticle(NP)vaccines can generate a more potent immune response than mRNA vaccines[2].

Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2,which also can cross・transmit to many animals but not mice.Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection.Although neither is the natural situation,they are currently utilized to establish mouse infection models.Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice.The SARS-CoV-2(B.1.351)re plicated efficiently and induced significant pathological changes in lungs and tracheas,accompanied by elevated proinflammatory cytokines in the lungs and sera.Mechanistically,the receptor-binding domain(RBD)of SARS-CoV-2(B.1.351)spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2(mACE2),allowing the mice highly susceptible to SARS-CoV-2(B.1.351)infection.Our work suggests that SARS-CoV-2(B.1.351)expands the host range and therefore increases its transmission route without adapted mutation.As the wild house mice live with human populations quite closely,this possible transmission route could be potentially risky.In addition,because SARS-CoV-2(B.1.351)is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated,the SARS-CoV-2(B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.