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1.
Cell ; 2022.
Article in English | ScienceDirect | ID: covidwho-1803705

ABSTRACT

Summary Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants, and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

2.
MedComm ; 3(2), 2022.
Article in English | EuropePMC | ID: covidwho-1790141

ABSTRACT

In view of the rapid development of the COVID‐19 pandemic and SARS‐CoV‐2 mutation, we characterized the emerging SARS‐CoV‐2 variants of concern (VOCs) by both bioinformatics methods and experiments. The representative genomic sequences of SARS‐CoV‐2 VOCs were first downloaded from NCBI, including the prototypic strain, Alpha (B.1.1.7) strain, Beta (B.1.351) strain, Delta (B.1.617.2), and Omicron (B1.1.529) strain. Bioinformatics analysis revealed that the D614G mutation led to formation of a protruding spike (S) in the tertiary structure of spike protein, which could be responsible for the enhanced binding to angiotensin‐converting enzyme 2 (ACE2) receptor. The epitope analysis further showed that the S protein antigenicity of the Omicron variant changed dramatically, which was possibly associated with its enhanced ability of immune escape. To verify the bioinformatics results, we performed experiments of pseudovirus infection and protein affinity assay. Notably, we found that the spike protein of Omicron variant showed the weakest infectivity and binding ability among all tested strains. Finally, we also proved this through virus infection experiments, and found that the cytotoxicity of Omicron seems to be not strong enough. The results in this study provide guidelines for prevention and control of COVID‐19. In this study, we first predicted and compared the structure of the S protein and B‐cell epitopes of different SARS‐CoV‐2 variants. Then, the binding ability of different SARS‐CoV‐2 variant S proteins to angiotensin‐converting enzyme 2 (ACE2) cells and the affinity of RBD region to ACE2 were further compared through pseudovirus infection and intermolecular binding ability test. Finally, cell infection experiments were performed. The results unexpectedly showed that Omicron possesses lower ACE2 binding capacity, and lower replication capacity than Delta strain.

3.
MedComm ; 3(2):e129, 2022.
Article in English | Wiley | ID: covidwho-1782643

ABSTRACT

In view of the rapid development of the COVID-19 pandemic and SARS-CoV-2 mutation, we characterized the emerging SARS-CoV-2 variants of concern (VOCs) by both bioinformatics methods and experiments. The representative genomic sequences of SARS-CoV-2 VOCs were first downloaded from NCBI, including the prototypic strain, Alpha (B.1.1.7) strain, Beta (B.1.351) strain, Delta (B.1.617.2), and Omicron (B1.1.529) strain. Bioinformatics analysis revealed that the D614G mutation led to formation of a protruding spike (S) in the tertiary structure of spike protein, which could be responsible for the enhanced binding to angiotensin-converting enzyme 2 (ACE2) receptor. The epitope analysis further showed that the S protein antigenicity of the Omicron variant changed dramatically, which was possibly associated with its enhanced ability of immune escape. To verify the bioinformatics results, we performed experiments of pseudovirus infection and protein affinity assay. Notably, we found that the spike protein of Omicron variant showed the weakest infectivity and binding ability among all tested strains. Finally, we also proved this through virus infection experiments, and found that the cytotoxicity of Omicron seems to be not strong enough. The results in this study provide guidelines for prevention and control of COVID-19.

4.
Protein Cell ; 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1777862

ABSTRACT

The nucleocapsid (N) protein of SARS-CoV-2 has been reported to have a high ability of liquid-liquid phase separation, which enables its incorporation into stress granules (SGs) of host cells. However, whether SG invasion by N protein occurs in the scenario of SARS-CoV-2 infection is unknow, neither do we know its consequence. Here, we used SARS-CoV-2 to infect mammalian cells and observed the incorporation of N protein into SGs, which resulted in markedly impaired self-disassembly but stimulated cell cellular clearance of SGs. NMR experiments further showed that N protein binds to the SG-related amyloid proteins via non-specific transient interactions, which not only expedites the phase transition of these proteins to aberrant amyloid aggregation in vitro, but also promotes the aggregation of FUS with ALS-associated P525L mutation in cells. In addition, we found that ACE2 is not necessary for the infection of SARS-CoV-2 to mammalian cells. Our work indicates that SARS-CoV-2 infection can impair the disassembly of host SGs and promote the aggregation of SG-related amyloid proteins, which may lead to an increased risk of neurodegeneration.

5.
Protein Cell ; 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1773029

ABSTRACT

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.

6.
IUBMB Life ; 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1772709

ABSTRACT

Coronavirus disease 2019, a newly emerging serious infectious disease, has spread worldwide. To date, effective drugs against the disease are limited. Traditional Chinese medicine was commonly used treating COVID-19 patients in China. Here we tried to identify herbal effective lipid compounds from the lipid library of 92 heat-clearing and detoxication Chinese herbs. Through virtual screening, enzymatic activity and inhibition assays and surface plasmon resonance tests, we identified lipid compounds targeting the main protease (Mpro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and verified their functions. Here, we found that natural lipid compounds LPC (14:0/0:0) and LPC (16:0/0:0) could target SARS-CoV-2 Mpro , recover cell death induced by SARS-CoV-2, and ameliorate acute lung injury (ALI) / acute respiratory distress syndrome (ARDS) induced by bacterial lipopolysaccharides and virus poly (I:C) mimics in vivo and in vitro. Our results suggest that LPC (14:0/0:0) and LPC (16:0/0:0) might be potential pan remedy against ARDS. This article is protected by copyright. All rights reserved.

7.
Cell ; 2022.
Article in English | ScienceDirect | ID: covidwho-1767964

ABSTRACT

Summary As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine, and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

8.
Signal Transduct Target Ther ; 7(1): 61, 2022 02 25.
Article in English | MEDLINE | ID: covidwho-1758178

ABSTRACT

Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2. To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants, we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine, followed by challenging with emerging SARS-CoV-2 variants of concern (VOCs). These vaccinated animals produced neutralizing antibodies against Alpha, Beta, Delta, and Omicron variants, although there were certain declinations of geometric mean titer (GMT) as compared with prototypic SARS-CoV-2. Of note, in vivo this prototypic vaccine not only reduced the viral loads in nasal, throat and anal swabs, pulmonary tissues, but also improved the pathological changes in the lung infected by variants of Alpha, Beta, and Delta. In summary, the prototypic SARS-CoV-2 inactivated vaccine in this study protected against VOCs to certain extension, which is of great significance for prevention and control of COVID-19.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Cross Protection , SARS-CoV-2/drug effects , Vaccination/methods , Vaccines, Inactivated/administration & dosage , Anal Canal/virology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , Humans , Immunogenicity, Vaccine , Lung/virology , Macaca mulatta , Male , Nasal Cavity/virology , Pharynx/virology , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/virology , Viral Load/drug effects
9.
Signal Transduct Target Ther ; 7(1): 69, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721495

ABSTRACT

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world. To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain (RBD) (PS-RBD) and whole inactivated virus particle vaccine (IV) against the variant strains, in this study, rhesus macaques were immunized with PS-RBD or IV vaccine, followed by a Beta variant (B.1.351) challenge. Although neutralizing activity against the Beta variant was reduced compared with that against the prototype, the decreased viral load in both upper and lower respiratory tracts, milder pathological changes, and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model. Furthermore, PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha, Beta, Delta, and Omicron variants in our study, though the neutralizing antibody (NAb) titers declined by varying degrees, demonstrating potential protection of PS-RBD against current circulating variants of concern (VOCs). Interestingly, although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant, it still showed reduction for viral load and significantly alleviated pathological change. Other correlates of vaccine-induced protection (CoP) like antibody-dependent cellular cytotoxicity (ADCC) and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Humans , Macaca mulatta , Vaccines, Inactivated/immunology , Vaccines, Inactivated/pharmacology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacology
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325084

ABSTRACT

The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

12.
Signal Transduct Target Ther ; 6(1): 439, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585883

ABSTRACT

The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans. Briefly, human ACE2-transgenic (hACE2) mice were intratracheally instilled with the formaldehyde-inactivated SARS-CoV-2, resulting in a rapid weight loss and detrimental changes in lung structure and function. The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation, hemorrhage, necrotic debris, and hyaline membrane formation. The production of fatal cytokines (IL-1ß, TNF-α, and IL-6) and the infiltration of activated neutrophils, inflammatory monocyte-macrophages, and T cells in the lung were also determined, suggesting the activation of an adaptive immune response. Therapeutic strategies, such as dexamethasone or passive antibody therapy, could effectively ameliorate the disease progression in this model. Therefore, the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , COVID-19/immunology , Lung/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/genetics , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Respiratory Distress Syndrome/genetics
13.
MedComm ; 2021.
Article in English | EuropePMC | ID: covidwho-1567359

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the etiology of coronavirus disease 2019 (COVID‐19) pandemic. Current variants including Alpha, Beta, Gamma, Delta, and Lambda increase the capacity of infection and transmission of SARS‐CoV‐2, which might disable the in‐used therapies and vaccines. The COVID‐19 has now put an enormous strain on health care system all over the world. Therefore, the development of animal models that can capture characteristics and immune responses observed in COVID‐19 patients is urgently needed. Appropriate models could accelerate the testing of therapeutic drugs and vaccines against SARS‐CoV‐2. In this review, we aim to summarize the current animal models for SARS‐CoV‐2 infection, including mice, hamsters, nonhuman primates, and ferrets, and discuss the details of transmission, pathology, and immunology induced by SARS‐CoV‐2 in these animal models. We hope this could throw light to the increased usefulness in fundamental studies of COVID‐19 and the preclinical analysis of vaccines and therapeutic agents. Animal models that recapitulate characteristics and immune responses observed in COVID‐19 patients are urgently needed. These animal models such as mouse, hamster, nonhuman primate, and ferret, have provided robust platforms for studying the transmission, pathogenesis, and immunology induced by SARS‐CoV‐2, and for evaluating the immunomodulatory and antiviral drugs and vaccines against COVID‐19.

14.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1556321

ABSTRACT

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Subject(s)
Antiviral Agents/administration & dosage , Azides/administration & dosage , COVID-19/drug therapy , Deoxycytidine/analogs & derivatives , SARS-CoV-2/metabolism , Thymus Gland , Adult , Aged , Aged, 80 and over , Animals , Coronavirus OC43, Human/metabolism , Deoxycytidine/administration & dosage , Female , Humans , Male , Middle Aged , Rats , Thymus Gland/metabolism , Thymus Gland/virology
15.
Signal Transduct Target Ther ; 6(1): 406, 2021 11 23.
Article in English | MEDLINE | ID: covidwho-1532031

ABSTRACT

Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.


Subject(s)
Brain , COVID-19 , Nervous System Diseases , SARS-CoV-2/metabolism , Brain/metabolism , Brain/pathology , Brain/virology , COVID-19/complications , COVID-19/metabolism , COVID-19/pathology , Humans , Nervous System Diseases/etiology , Nervous System Diseases/metabolism , Nervous System Diseases/pathology , Nervous System Diseases/virology
18.
Nano Lett ; 21(14): 5920-5930, 2021 07 28.
Article in English | MEDLINE | ID: covidwho-1316697

ABSTRACT

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Animals , COVID-19 Vaccines , Humans , Mice , Protein Binding , SARS-CoV-2
19.
Front Immunol ; 12: 697074, 2021.
Article in English | MEDLINE | ID: covidwho-1311376

ABSTRACT

The development of a safe and effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we aim to develop novel SARS-CoV-2 vaccines based on a derivative of less commonly used rare adenovirus serotype AdC68 vector. Three vaccine candidates were constructed expressing either the full-length spike (AdC68-19S) or receptor-binding domain (RBD) with two different signal sequences (AdC68-19RBD and AdC68-19RBDs). Single-dose intramuscular immunization induced robust and sustained binding and neutralizing antibody responses in BALB/c mice up to 40 weeks after immunization, with AdC68-19S being superior to AdC68-19RBD and AdC68-19RBDs. Importantly, immunization with AdC68-19S induced protective immunity against high-dose challenge with live SARS-CoV-2 in a golden Syrian hamster model of SARS-CoV-2 infection. Vaccinated animals demonstrated dramatic decreases in viral RNA copies and infectious virus in the lungs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in rhesus macaques. Taken together, these results confirm that AdC68-19S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.


Subject(s)
Adenovirus Vaccines/administration & dosage , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Immunization Schedule , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccination/methods , Adenovirus Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , Mice , Mice, Inbred BALB C , Pan troglodytes , RNA, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , Transfection , Treatment Outcome
20.
Signal Transduct Target Ther ; 6(1): 213, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249203

ABSTRACT

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Humans , Immunogenicity, Vaccine/immunology , Lymphocyte Activation/immunology , Mice , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Th1 Cells/immunology , Th1 Cells/virology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/immunology
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