42 results about "Broadly neutralizing antibody" patented technology

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

The present application relates to epitope-targeted SIV and HIV vaccines. The invention provides novel envelope glycoproteins which may be utilized as HIV-1 vaccine immunogens, antigens for crystallization, and for identification of broadly neutralizing antibodies. The invention encompasses preparation and purification of immunogenic compositions which are formulated into vaccines of the present invention.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Unlike historical controls, where 3BNC117 and 10-1074 expression is lost within the first 4-5 weeks, 2 macaques maintained 10-1074 expression and 1 macaque maintained 3BNC117 for the duration of the trial. Anti-3BNC117 antibodies were only observed in 2 of the 3 macaques and were significantly delayed. Anti-10-1074 antibody responses were a log lower than typically observed in historic controls. The use of hydroxychloroquine as a pretreatment for AAV inoculation is a promising strategy. The significant decrease in anti-10-1074 antibody levels and the successful delivery of 10-1074 in 2 macaques and 3BNC117 in 1 macaque was very encouraging. Extending the dosage of hydroxychloroquine beyond 3 doses may be sufficient to observe long-term bNAb expression in all animals and further decrease ADA responses. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.

This invention belongs to the field of biotechnology, specifically relating to a broad-spectrum neutralizing antibody against porcine epidemic diarrhea virus (PEDV) and its applications. This invention screened a broad-spectrum neutralizing antibody against PEDV, 6G2. Cell model evaluation revealed that the antibody effectively blocked infection of cells by several highly prevalent PEDV genotypes: G1a, G1b, G2a, G2b, G2c, and S-INDEL. Further animal infection experiments in pigs demonstrated that the neutralizing antibody provided by this invention has good preventive and therapeutic effects against PEDV, which is of great significance for improving the ability of pig farms to control PEDV.

Disclosed are monoclonal antibodies, antigen binding fragments, and multi-specific antibodies that specifically bind a coronavirus spike protein, such as SARS-CoV-2. Also disclosed is the use of these antibodies and multi-specific antibodies for inhibiting a coronavirus infection, such as a SARS-CoV-2 infection. In addition, disclosed are methods for detecting a coronavirus, such as SARS-CoV-2, in a biological sample, using the disclosed antibodies and multi-specific antibodies.

The instant disclosure provides antibodies and antigen-binding fragments thereof that can bind to an influenza virus neuraminidase (NA) and can neutralize an influenza virus infection. Also provided are polynucleotides that encode an antibody, vectors that comprise such polynucleotides, host cells that can express the antibodies, related compositions, and methods of using the herein disclosed compositions to, for example, treat or prevent an influenza infection.

The invention provides broadly neutralizing antibodies directed to epitopes of Human Immunodeficiency Virus, or HIV. The invention further provides compositions containing HIV antibodies used for prophylaxis, and methods for diagnosis and treatment of HIV infection.

This invention belongs to the field of biomedical technology, specifically relating to an antigenic epitope peptide combination for a broad-spectrum novel coronavirus vaccine and its application. The antigenic epitope peptide combination of this invention includes a combination of viral spike protein Epi-I antigenic epitope peptides, a combination of viral spike protein Epi-II antigenic epitope peptides, and a combination of viral spike protein Epi-III antigenic epitope peptides. These antigenic epitope peptide combinations are obtained by screening spike protein epitopes from three broad-spectrum neutralizing antibodies against SARS-CoV-2, and can induce a broad-spectrum neutralizing antibody response in the host, used for the preparation of a broad-spectrum novel coronavirus vaccine. Using the antigenic epitope peptide combination of this invention, an antigenic epitope fusion protein L9 was obtained and prepared into a vaccine. The results of the examples show that the L9 vaccine has a better neutralizing effect against SARS-CoV-2 variants than the control group of the Wuhan strain of SARS-CoV-2 spike protein RBD, exhibiting good cross-neutralization.

The present disclosure relates to monoclonal human antibodies, or binding fragments thereof, directed against the CD4 binding site of human immunodeficiency virus HIV-1, pharmaceutical compositions comprising such monoclonal human antibodies, or binding fragments thereof, kits comprising such antibodies, or binding fragments thereof, and monoclonal antibodies or binding fragments thereof as well as pharmaceutical compositions and kits for use as medicaments and for the treatment or prevention of diseases caused by human immunodeficiency virus HIV-1.

The present disclosure provides antibodies and antigen-binding fragments that are capable of binding to RSV and / or MPV fusion glycoproteins and that are capable of neutralizing RSV and / or MPV infection. Also provided are polynucleotides encoding the antibodies, vectors comprising such polynucleotides, host cells capable of expressing these antibodies, related compositions, and methods of using the compositions disclosed herein, for example, to treat or prevent RSV and / or MPV infection.

The invention relates to an anti-HIV broad-spectrum neutralizing antibody with an ADCC effect and application of the anti-HIV broad-spectrum neutralizing antibody in treatment and / or prevention of HIV infected diseases. The antibody FD22 disclosed by the invention shows broad-spectrum and strong neutralizing capacity on different subtype HIV-1 pseudoviruses which are prevalent globally, and particularly shows excellent neutralizing activity on HIV-1AE and BC subtype strains which are prevalent widely in China. The antibody FD22 is an effective supplement for the existing HIV neutralizing antibody drug library, and can provide more comprehensive prevention and treatment choices for Chinese epidemic strains. Meanwhile, the antibody FD22 can promote expression of NK cell activating factors, activate NK cells and improve the degranulation effect of the NK cells, so that the killing effect of immune cells such as the NK cells on HIV infected cells is enhanced, and the potential of treating HIV infection is shown.

Methods of identifying virus antigens are provided. In particular the antigens induce broadly neutralizing antibodies in Hepatitis C virus infections. Compositions for inducing an immune response are identified by the methods described herein.

The present invention relates to monoclonal human antibodies or binding fragments thereof directed against the V3 glycan site of human immunodeficiency virus HIV-1, pharmaceutical compositions comprising such monoclonal human antibodies or binding fragments thereof, kits comprising such antibodies or binding fragments thereof, pharmaceutical compositions comprising such antibodies or binding fragments thereof, pharmaceutical compositions comprising such antibodies or binding fragments thereof, pharmaceutical compositions comprising such antibodies or binding fragments thereof, pharmaceutical compositions comprising such antibodies or binding fragments thereof, and pharmaceutical compositions comprising such antibodies or binding fragments thereof. And monoclonal antibodies or binding fragments thereof as well as pharmaceutical compositions and kits for use as medicaments and for the treatment or prevention of diseases caused by human immunodeficiency virus HIV-1.

The invention belongs to the field of biological medicine, and particularly relates to novel application of a functional regulator of xylosyltransferase 1 (XYLT1) in preparation of drugs for resisting human immunodeficiency virus (HIV) infection and / or resisting tumor immunotherapy. In-vitro experiments prove that up-regulation of expression or activity of XYLT1 can inhibit HIV virus replication (such as reduction of p24 antigen and virus infectivity) and enhance the curative effect of a broad-spectrum neutralizing antibody (such as 3BNC117); meanwhile, the XYLT1 can mediate the degradation of PD-L1 protein, relieve the inhibition on T cells and enhance the anti-tumor killing activity of CD8T cells. The invention provides a new target spot and a combined treatment strategy for immunotherapy of viral diseases and tumors.

The present invention relates to anti-HIV antibodies. Also disclosed are related methods and compositions. HIV causes acquired immunodeficiency syndrome (AIDS), a condition in humans characterized by clinical features including wasting syndromes, central nervous system degeneration and profound immunosuppression that results in life-threatening opportunistic infections and malignancies. Since its discovery in 1981, HIV type 1 (HIV-1) has led to the death of at least 25 million people worldwide.

The invention discloses a monoclonal antibody of Japanese encephalitis virus and Zika virus and application of the monoclonal antibody, and belongs to the technical field of immunology and molecular virology. The monoclonal antibody or the antigen binding fragment thereof comprises VH CDR1, VH CDR2 and VH CDR3 of which the amino acid sequences are shown as SEQ ID NO: 1-3, and VL CDR1 and VL CDR3 of which the amino acid sequences are shown as SEQ ID NO: 4 and SEQ ID NO: 5, and the amino acid sequence is VL CDR2 of AAS. The monoclonal antibody LZY2086 provided by the invention can be combined with E protein extracellular regions of the encephalitis B virus and the Zika virus with high affinity, and has very strong neutralizing activity on the encephalitis B virus and the Zika virus. Therefore, as a broad-spectrum neutralizing antibody, the monoclonal antibody LZY2086 disclosed by the invention has ideal clinical application value in prevention and treatment of Japanese encephalitis virus and Zika virus infection.

The invention provides an HIV-1 Env-derived immunogen that simultaneously engages more than one lineage of germline bNAbs specific for different neutralization target sites of the native HIV-1 Env trimer. In certain embodiments, the inventive immunogen comprises a chimeric Env, with binding sites drawn from more than one native Env proteins. These can be used both in the form of full-length / minimally truncated membrane-bound trimers (e.g., expressed from cDNA, mRNA or viral vectors, which also are provided by the present invention, as are cells comprising the immunogen) or, alternatively, in the form of soluble truncated trimers (e.g., SOSIP or IP trimers). Also provided are a pharmaceutical composition comprising the inventive immunogen, nucleic acids encoding the same, and / or cells comprising them, and a method of vaccinating a human patient against HIV using the inventive immunogen and composition.

The present invention relates to the field of vaccination, in particular, of vaccination against hepatitis C virus (HCV). The present invention provides a composition comprising at least parts of the HCV core protein, and HCV E1 and HCV E2 protein of a specific HCV strain, as well as VSV-G protein. The proteins may be assembled in rVSV-HCV particles. This has been identified to induce particularly advantageous broadly neutralizing antibodies. The invention further provides nucleic acids encoding said HCV proteins and VSV proteins but not encoding VSV-G protein. Vaccines comprising the particles, compositions or nucleic acids are disclosed as useful, in particular, for prophylactic vaccination against HCV. Methods of producing the rVSV-HCV particles or compositions of the invention and the produced particles and compositions are also subject-matter of the invention.

A method is described herein comprising training a protein language model using a first dataset to predict neutralization values of individual antibody sequences against corresponding Env sequences, using the trained model on a second dataset to identify neutralizing values of individual antibody sequences in the second dataset against Env sequences in a virus panel, summing the identified neutralization values of antibodies in the second dataset to identify a first set of broadly neutralizing antibody (bnAb) precursors, wherein an antibody sequence qualifies as a precursor when its summed neutralization values exceed a threshold, structurally comparing the first set of bnAb precursors to a known bnAb, using information of the structural comparison to identify a second set of bnAb precursors, maturing the second set of precursors to breadth, and identifying immunogens that select for the matured precursors.

The instant disclosure provides antibodies and antigen-binding fragments that can bind to a RSV and / or MPV fusion glycoprotein and can neutralize a RSV and / or MPV infection. Also provided are polynucleotides that encode an antibody, vectors that comprise such polynucleotides, host cells that can express the antibodies, related compositions, and methods of using the herein disclosed compositions to, for example, treat or prevent a RSV and / or MPV infection.

The application discloses a broad-spectrum neutralizing antibody W328-6H2 against coronavirus and application thereof in preparation of vaccines. The application provides an IgG antibody, named W328-6H2 antibody, which is composed of a light chain and a heavy chain; CDR1, CDR2 and CDR3 in a heavy chain variable region in the heavy chain are sequentially shown as positions 45-52, 70-77 and 116-131 in SEQ ID NO:1; CDR1, CDR2 and CDR3 in a light chain variable region in the light chain are sequentially shown as positions 46-56, 74-76 and 113-121 in SEQ ID NO:3. The W328-6H2 antibody not only has the effect of neutralizing atypical pneumonia virus, but also has broad-spectrum neutralizing activity on other coronaviruses. The application has great application value for prevention and control of beta genus coronavirus and will have far-reaching social significance.

The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.

The invention relates to proteins and nucleic acids for immunization regimens, in particular, immunogens that can prime rare bnAb precursor B cells and guide their maturation towards bnAbs capable of neutralizing diverse HIV strains, modifications thereof, and / or development of nanoparticles, and / or development of membrane-anchored immunogens, and methods of making and using the same. The invention also encompasses cell surface trimers that bind to the broadly neutralizing antibodies and / or nucleic acids encoding the same.

The invention relates to proteins and nucleic acids for immunization regimens, in particular, immunogens that can prime rare bnAb precursor B cells and guide their maturation towards bnAbs capable of neutralizing diverse HIV strains, modifications thereof, and / or development of nanoparticles, and / or development of membrane-anchored immunogens, and methods of making and using the same. The invention also encompasses cell surface trimers that bind to the broadly neutralizing antibodies and / or nucleic acids encoding the same.

The invention relates to a lentiviral vector or retroviral vector and application thereof in infection of B cells, establishment of acquired immunity in subjects and preparation of broad-spectrum neutralizing antibodies. A virus envelope of the lentiviral vector or the retroviral vector contains a targeting molecule targeting B cells and carries a broad-spectrum neutralizing antibody gene; the viral glycoprotein of the lentiviral vector or retroviral vector may further comprise a first mutation that attenuates its ability to bind to a receptor and a second mutation that enhances its ability to antagonize complement inactivation, the capacity of the lentiviral vector or the retroviral vector for targeted transduction of B cells in a subject and preparation of broad-spectrum neutralizing antibodies is further enhanced.

The present disclosure provides novel broadly neutralizing anti-tick-borne encephalitis virus (TBEV) antibodies. Anti-TBEV antibodies are induced by various tick-borne flaviviruses, including TBEV. These represent novel therapeutic strategies for preventing or treating the associated diseases or infections.