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1.
Viruses ; 14(6):1162, 2022.
Article in English | MDPI | ID: covidwho-1869818

ABSTRACT

Over the years, infectious diseases with high morbidity and mortality disrupted human healthcare systems and devastated economies globally. Respiratory viruses, especially emerging or re-emerging RNA viruses, including influenza and human coronavirus, are the main pathogens of acute respiratory diseases that cause epidemics or even global pandemics. Importantly, due to the rapid mutation of viruses, there are few effective drugs and vaccines for the treatment and prevention of these RNA virus infections. Of note, a class of antibodies derived from camelid and shark, named nanobody or single-domain antibody (sdAb), was characterized by smaller size, lower production costs, more accessible binding epitopes, and inhalable properties, which have advantages in the treatment of respiratory diseases compared to conventional antibodies. Currently, a number of sdAbs have been developed against various respiratory RNA viruses and demonstrated potent therapeutic efficacy in mouse models. Here, we review the current status of the development of antiviral sdAb and discuss their potential as therapeutics for respiratory RNA viral diseases.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335007

ABSTRACT

The continuous emergence of novel SARS-CoV-2 variants poses new challenges to the fight against the COVID-19 pandemic. The newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over the world. The development of antibody targeting conserved and universal epitope is urgently needed. A subset neutralizing antibody(nAbs) against COVID-19 from convalescent patients were isolated in our previous study. Here in this study, we investigated the accommodation of these nAbs to SARS-CoV-2 variants of concerns (VOCs), revealing that IgG 553-49 neutralizes pseudovirus of SARS-CoV-2 Omicron variant. In addition, we determined the cryo-EM structure of SARS-CoV-2 spike complexed with three antibodies targeting different epitopes, including 553-49, 553-15 and 553-60. Notably, 553-49 targets a novel conserved epitope and neutralizes virus by disassembling spike trimers. 553-15, an antibody that neutralizes all the other VOCs except omicron, cross-links two spike trimers to form trimer dimer, demonstrating that 553-15 neutralizes virus by steric hindrance and virion aggregation. These findings suggest the potential to develop 49 and other antibody targeting this highly conserved epitope as promising cocktail therapeutics reagent for COVID-19.

3.
Cell ; 185(8): 1389-1401.e18, 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1788017

ABSTRACT

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have been limited by the continuous emergence of viral variants and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.


Subject(s)
COVID-19 Vaccines , Single-Domain Antibodies , Administration, Inhalation , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , COVID-19 Vaccines/administration & dosage , Disease Models, Animal , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
4.
Mol Immunol ; 145: 3-16, 2022 05.
Article in English | MEDLINE | ID: covidwho-1783652

ABSTRACT

In the early 1960's the first human coronaviruses (designated 229E and OC43) were identified as etiologic agents of the common cold, to be followed by the subsequent isolation of three more human coronaviruses similarly associated with cold-like diseases. In contrast to these "mild" coronaviruses, over the last 20 years there have been three independent events of emergence of pandemic severe and acute life-threatening respiratory diseases caused by three novel beta-coronaviruses, SARS CoV, MERS CoV and most recently SARS CoV2. Whereas the first SARS CoV appeared in November 2002 and spontaneously disappeared by the summer of 2003, MERS CoV has continued persistently to spill over to humans via an intermediary camel vector, causing tens of cases annually. Although human-to-human transmission is rare, the fatality rate of MERS CoV disease is remarkably higher than 30%. COVID-19 however, is fortunately much less fatal, despite that its etiologic agent, SARS CoV2, is tremendously infectious, particularly with the recent evolution of the Omicron variants of concern (BA.1 and BA.2). Of note, MERS CoV prevalence in camel populations in Africa and the Middle East is extremely high. Moreover, MERS CoV and SARS CoV2 co-exist in the Middle East and especially in Saudi Arabia and the UAE, where sporadic incidences of co-infection have already been reported. Co-infection, either due to reverse spill-over of SARS CoV2 to camels or in double infected humans could lead to recombination between the two viruses, rendering either SARS CoV2 more lethal or MERS CoV more transmittable. In an attempt to prepare for what could develop into a catastrophic event, we have focused on developing a novel epitope-based immunogen for MERS CoV. Implementing combinatorial phage-display conformer libraries, the Receptor Binding Motif (RBM) of the MERS CoV Spike protein has been successfully reconstituted and shown to be recognized by a panel of seven neutralizing monoclonal antibodies.


Subject(s)
COVID-19 , Coinfection , Middle East Respiratory Syndrome Coronavirus , Humans , SARS-CoV-2
5.
Emerg Microbes Infect ; 11(1): 1186-1190, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1774289

ABSTRACT

In the fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), monoclonal antibodies (mAbs) serve as key strategies for the rapid prevention and treatment of COVID-19. However, analysis to fully characterize functional SARS-CoV-2 mAbs is still needed. In this study, by interrogating 1,695 published or patented mAbs of human origin and validated SARS-CoV-2-binding potency, we found a highly preferential usage of IGHV3-53/3-66 germline genes that was then revealed as a distinct selectivity of SARS-CoV-2-induced humoral immunity across other coronaviruses. Moreover, among the rare somatic hypermutations, we identified a novel mutation signature of F27 to I, L, or V with high frequency, which was located in the CDR1 region of the heavy chain among IGHV3-53/3-66-encoded antibodies. This convergent mutation contributed to improving SARS-CoV-2 binding affinity and may advance our knowledge of the humoral immunity to SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Humans , Immunity, Humoral , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315723

ABSTRACT

The pandemic of COVID-19 caused by SARS-CoV-2 has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to ACE2 receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296391

ABSTRACT

mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293476

ABSTRACT

mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.

9.
J Am Chem Soc ; 143(47): 19794-19801, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1521695

ABSTRACT

Effective screening of infectious diseases requires a fast, cheap, and population-scale testing. Antigen pool testing can increase the test rate and shorten the screening time, thus being a valuable approach for epidemic prevention and control. However, the overall percent agreement (OPA) with polymerase chain reaction (PCR) is one-half to three-quarters, hampering it from being a comprehensive method, especially pool testing, beyond the gold-standard PCR. Here, a multiantibodies transistor assay is developed for sensitive and highly precise antigen pool testing. The multiantibodies capture SARS-CoV-2 spike S1 proteins with different configurations, resulting in an antigen-binding affinity down to 0.34 fM. The limit of detection reaches 3.5 × 10-17 g mL-1SARS-CoV-2 spike S1 protein in artificial saliva, 4-5 orders of magnitude lower than existing transistor sensors. The testing of 60 nasopharyngeal swabs exhibits ∼100% OPA with PCR within an average diagnoses time of 38.9 s. Owing to its highly precise feature, a portable integrated platform is fabricated, which achieves 10-in-1 pooled screening for high testing throughput. This work solves the long-standing problem of antigen pool testing, enabling it to be a valuable tool in precise diagnoses and population-wide screening of COVID-19 or other epidemics in the future.


Subject(s)
Antibodies/immunology , Immunoassay/methods , Spike Glycoprotein, Coronavirus/immunology , Transistors, Electronic , COVID-19/diagnosis , COVID-19/virology , Immunoassay/instrumentation , Limit of Detection , Nasopharynx/virology , Polymerase Chain Reaction , Protein Subunits/genetics , Protein Subunits/immunology , Protein Subunits/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Saliva/virology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
10.
Signal Transduct Target Ther ; 6(1): 378, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1500450

ABSTRACT

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , COVID-19 , SARS-CoV-2/chemistry , Single-Chain Antibodies/chemistry , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Crystallography, X-Ray , Epitopes/chemistry , Epitopes/immunology , Humans , Mice , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Single-Chain Antibodies/therapeutic use
11.
Nano Lett ; 21(19): 7897-7904, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1440453

ABSTRACT

The fast spread of SARS-CoV-2 has severely threatened the public health. Establishing a sensitive method for SARS-CoV-2 detection is of great significance to contain the worldwide pandemic. Here, we develop a graphene field-effect transistor (g-FET) biosensor and realize ultrasensitive SARS-CoV-2 antibody detection with a limit of detection (LoD) down to 10-18 M (equivalent to 10-16 g mL-1) level. The g-FETs are modified with spike S1 proteins, and the SARS-CoV-2 antibody biorecognition events occur in the vicinity of the graphene surface, yielding an LoD of ∼150 antibodies in 100 µL full serum, which is the lowest LoD value of antibody detection. The diagnoses time is down to 2 min for detecting clinical serum samples. As such, the g-FETs leverage rapid and precise SARS-CoV-2 screening and also hold great promise in prevention and control of other epidemic outbreaks in the future.


Subject(s)
Biosensing Techniques , COVID-19 , Graphite , Humans , Limit of Detection , SARS-CoV-2
14.
Acta Pharm Sin B ; 12(4): 1591-1623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1293568

ABSTRACT

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

15.
Virol Sin ; 36(5): 934-947, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293454

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446-S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Humans , Spike Glycoprotein, Coronavirus
16.
Antib Ther ; 4(2): 89-98, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1262064

ABSTRACT

In recent years, fully human monoclonal antibodies (mAbs) are making up an increasing share of the pharmaceutical market. However, to improve affinity and efficacy of antibodies, many somatic hypermutations could be introduced during affinity maturation, which cause several issues including safety and efficacy and limit their application in clinic. Here, we propose a special class of human mAbs with limited level of somatic mutations, referred to as germline-like mAbs. Remarkably, germline-like mAbs could have high affinity and potent neutralizing activity in vitro and in various animal models, despite lacking of extensive affinity maturation. Furthermore, the germline nature of these mAbs implies that they exhibit lower immunogenicity and can be elicited relatively fast in vivo compared with highly somatically mutated antibodies. In this review, we summarize germline-like mAbs with strong therapeutic and protection activity against various viruses that caused large-scale outbreaks in the last decade, including influenza virus H7N9, Zika virus, Dengue virus, Middle East respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus 2. We also illustrate underlying molecular mechanisms of these germline-like antibodies against viral infections from the structural and genetic perspective, thus providing insight into further development as therapeutic agents for the treatment of infectious diseases and implication for rational design of effective vaccines.

17.
Angewandte Chemie ; n/a(n/a), 2021.
Article in English | Wiley | ID: covidwho-1135068

ABSTRACT

SARS-CoV-2 attaches to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS-CoV-2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD-based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331 and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to deciphering carbohydrate structure?function relationships.

18.
Fundamental Research ; 2021.
Article in English | ScienceDirect | ID: covidwho-1062352

ABSTRACT

The worldwide pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late December 2019 requires the urgent development of therapeutic options. So far, numerous studies have investigated and uncovered the underlying epidemiology and clinical characteristics of COVID-19 infections in order to develop effective drugs. Compared with antiviral small-molecule inhibitors, biotherapeutics have unique advantages such as few side effects by virtue of their high specificity, and thus can be rapidly developed for promising treatments of COVID-19. Here, we summarize potential biotherapeutics and their mechanisms of action, including convalescent plasma, therapeutic antibodies, peptides, engineered ACE2, interferons, cytokine inhibitors, and RNAi-based therapeutics, and discuss in depth the advancements and precautions for each type of biotherapeutics in the treatment of COVID-19.

19.
Cell Rep ; 34(5): 108699, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1044918

ABSTRACT

Several potent neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been identified. However, antibody-dependent enhancement (ADE) has not been comprehensively studied for SARS-CoV-2, and the relationship between enhancing versus neutralizing activities and antibody epitopes remains unknown. Here, we select a convalescent individual with potent IgG neutralizing activity and characterize his antibody response. Monoclonal antibodies isolated from memory B cells target four groups of five non-overlapping receptor-binding domain (RBD) epitopes. Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcγ receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE, while antibodies against the fourth epitope group are poorly neutralizing. One antibody, XG014, potently cross-neutralizes SARS-CoV-2 variants, as well as SARS-CoV-1, with respective IC50 (50% inhibitory concentration) values as low as 5.1 and 23.7 ng/mL, while not exhibiting ADE. Therefore, neutralization and ADE of human SARS-CoV-2 antibodies correlate with non-overlapping RBD epitopes.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody-Dependent Enhancement , Epitopes/immunology , Adolescent , Adult , Aged , Antibodies, Monoclonal/immunology , Antibodies, Viral/therapeutic use , Antigen-Antibody Reactions , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Cell Line , Child , Cluster Analysis , Female , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Protein Domains/immunology , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Young Adult
20.
Signal Transduct Target Ther ; 5(1): 282, 2020 11 27.
Article in English | MEDLINE | ID: covidwho-947524

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.


Subject(s)
Antibodies, Neutralizing/pharmacology , COVID-19 Vaccines/pharmacology , COVID-19/drug therapy , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Epitopes/immunology , Humans , Immunoglobulin Fc Fragments/immunology , Immunoglobulin Fc Fragments/pharmacology , Mice , Mice, Inbred BALB C , Pandemics , Protein Binding/drug effects , Protein Binding/immunology , Receptors, Virus/genetics , Receptors, Virus/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors
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