69 results about "Memory B cell" 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 application relates to an antibody against monkeypox virus and a preparation method thereof, and the humanized monkeypox virus antibody H3-14A7 is obtained by screening memory B cells of a human antibody against H3 specific binding mouse. The H3-14A7 has the characteristics of strong monkeypox virus binding capacity, good in-vitro neutralization, large affinity and in-vivo protection.

Methods are described herein for screening an antibody producing cell within a microfluidic environment. The antibody producing cell may be a B cell lymphocyte, which may be a memory B cell or a plasma cell. An antigen of interest may be brought into proximity with the antibody producing cell and binding of the antigen by an antibody produced by the antibody producing cell may be monitored. Methods of obtaining a sequencing library from an antibody producing cell are also described.

The invention relates to the technical field of immunization. The invention discloses parabacteroides dieldrii and parabacteroides goldsteinii, an application of the parabacteroides dieldrii and / or the parabacteroides goldsteinii in preparation of an immunopotentiator of a vaccine, and the immunopotentiator of the vaccine, and particularly discloses the parabacteroides dieldrii and the parabacteroides goldsteinii, the application of the parabacteroides dieldrii and / or the parabacteroides goldsteinii in preparation of the immunopotentiator of the vaccine. The parabacteroides dieldrii and / or the parabacteroides gold can be used as an immunopotentiator, can activate immunity, enhance antibody titer and shorten antibody generation reaction time, and can remarkably promote proliferation of B cells, plasma cells and memory B cell subgroups in a hair growth center.

Provided are a set of fully human TSH receptor (TSHR)-blocking monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and single memory B cells that specifically recognize TSHR in peripheral blood of a patient with a high titer of TSH-blocking antibodies (TBAb), performing in vitro cloning of antibody light and heavy chains and performing recombinant expression, and using hTSHR-CHO cells to perform screening and validation of antibody properties to obtain a blocking monoclonal antibody that specifically targets human TSHR. The fully human TSH receptor-blocking monoclonal antibodies specifically bind to a TSHR, and effectively block signal transduction after a TSH binds to a receptor, inhibit the synthetic secretion of thyroid hormones, and significantly reduce and inhibit TSHR expression and fibrosis in orbital fibroblasts of effector cells associated with thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves' disease (GD) and other diseases caused by hyperthyroidism, such as thyroid eye disease (TED).

The invention relates to the field of antibody engineering, in particular to a monoclonal antibody specifically targeting a monkey pox virus and application of the monoclonal antibody. According to the invention, by screening mouse memory B cells specifically combined with monkey pox virus envelope protein A35R, monkey pox virus antibodies 1H4, 3H3, 3H6, 13H1 and 17H1 with high neutralization activity are obtained. Wherein 17H1 has excellent affinity and neutralizing efficacy on monkey pox virus and has a strong in-vivo protection effect, and 100% of survival rate of challenged mice is achieved in prevention and treatment experiments. The sequence of the antibody is completely different from that of an existing monkey pox virus antibody, and a new candidate product is provided for detection, diagnosis, prevention and treatment of the monkey pox virus.

The present invention relates to a separated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen binding domain, and the extracellular antigen binding domain comprises an antibody or antibody fragment that binds to a human CXC chemokine receptor type 5 (CXCR5) protein. The present invention further relates to nucleic acid molecules encoding the CAR of the present invention, genetically modified immune cells expressing the CAR of the present invention, preferably T cells, and the use of the cells in the treatment of medical conditions related to the presence of pathogenic cells expressing CXCR5, wherein the pathogenic cells expressing CXCR5 are preferably pathogenic mature B cells and / or memory B cells and / or pathogenic T cells and / or follicular helper T cells, particularly mature B cell non-Hodgkin lymphoma (B-NHL), T cell non-Hodgkin lymphoma, or autoantibody-dependent autoimmune diseases, preferably selected from systemic lupus erythematosus (SLE) or rheumatoid arthritis.

An isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a B Cell Maturation Antigen (BCMA) polypeptide. The CAR preferably binds an epitope comprising one or more amino acids of residues 13 to 32 of the N-terminus of human BCMA. Also disclosed is a nucleic acid molecule encoding the CAR of the invention, a genetically modified immune cell, preferably a T cell, expressing the CAR of the invention and the use of said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as a disease of plasma cells, memory B cells and / or mature B cells, in particular multiple myeloma, non-Hodgkin's lymphoma or autoantibody-dependent autoimmune diseases.

The invention discloses a novel benzothiazole compound as well as a preparation method and application thereof. According to the novel benzothiazole compound, through targeted activation of an RIG-I / OAS innate immune pathway, expression of key proteins and genes such as OAS1 and RIG-I can be rapidly up-regulated, secretion of type I interferon and proinflammatory factors is induced, and instant immune enhancement is achieved; more importantly, by performing long-term functional reprogramming on innate immune cells (such as mononuclear cells and dendritic cells), persistent'innate immune memory '(namely immune domestication) can be induced. The dual-action mechanism can significantly enhance the activation of antigen presenting cells and promote the generation and long-term maintenance of memory B cells and effector memory T cells, has no significant toxicity to liver functions, can be used as an immunologic adjuvant and an immunodomestication molecule of an RSV vaccine, can synergistically improve the vaccine-induced RSV specific antibody titer and neutralizing antibody level, and can be used for preparing an immunologic adjuvant for the RSV vaccine. Long-acting immune protection is provided, and a brand new solution is provided for research and development of RSV vaccines.

Provided herein are vaccine compositions for use in the stimulation of broad-spectrum memory B cell expansion in a patient that has been exposed or is at risk of exposure to an infectious agent of unknown etiology. The composition comprises IL-15 or an IL-15 analog and at least two toll-like receptor (TLR) agonists, wherein the agonists are targeted to different members of the TLR family. Further contemplated herein are compositions and methods of stimulating germinal B cell expansion in a patient, the composition comprising IL-15 or an IL-15 analog and a nucleic acid, wherein the nucleic acid encodes at least one immunogenic peptide, and wherein the composition is administered either subcutaneously or directly into a lymph node.

The invention discloses PDADMAC modified silicon dioxide mineralized foot-and-mouth disease virus-like particles as well as a preparation method and application thereof. The PDADMAC modified silicon dioxide mineralized foot-and-mouth disease virus-like particle (VLPs-SiO2) is a mineralized particle obtained by forming a silicon dioxide mineralized foot-and-mouth disease virus-like particle under the action of PDADMAC and then further modifying the silicon dioxide mineralized foot-and-mouth disease virus-like particle with PDADMAC, and the SiO2 mineralization rate of FMDV VLPs reaches 90% or above. The observation of a transmission electron microscope and a scanning electron microscope shows that the VLPS-SiO2 is spherical-like nano-particles with the particle size of 80-100 nm. According to the present invention, the level of FMDVVLPs ingestion by DC2.4 cells is increased by SiO2 mineralization, after the mice are immunized by nasal dripping, the specific antibody level in the serum of the VLPS-SiO2 immune group and the secretory IgA level in the lung, the cecum and the excrement are higher than the level of the FMDVVLPs immune group, and the levels of Tfh, Th1, Th2, memory B cells and memory T cells are increased. The invention provides an effective technical means for enhancing mucosal immune protection of the VLPs vaccine.

B cell proliferation and / or memory B cell formation / expansion can be enhanced by contacting MAIT cells with nogapendekin alfa invaxcept (N-803) to produce stimulated MAIT cells, which stimulate B cell proliferation and / or memory B cell formation / expansion. Such stimulation can be performed in the presence of antigen or antigen-presenting cells. In particularly contemplated embodiments, MAIT cell stimulation is performed in vitro to produce immunostimulatory compositions and vaccines, or in vivo to enhance immune responses in airway tissue. Most typically, in vivo immune stimulation is performed by inhalation or intranasal delivery of a composition comprising N-803 and, optionally, vaccine components.

This invention relates to the field of immunology, specifically to a method for inducing the formation of memory B cells in vitro and its uses, and particularly to the in vitro screening of drugs that promote or inhibit the formation of memory B cells based on the method.

The invention relates to a humanized monoclonal antibody aiming at monkey pox virus and application of the humanized monoclonal antibody, human monkey pox virus antibodies B6R-16A1, B6R-21G7, B6R-22D12, B6R-22F9 and B6R-22H1 with high neutralization activity are obtained by screening memory B cells specifically combined with anti-B6R of a human antibody humanized mouse, and the human monkey pox virus antibodies have high neutralization activity. The monkey pox virus vaccine has the characteristics of strong combining capacity with monkey pox virus, good in-vitro neutrality, large affinity and in-vivo protection effect.

This application relates to humanized monoclonal antibodies against monkeypox virus and their applications. By screening humanized mouse anti-B6R specific binding memory B cells with fully human antibodies, humanized high-neutralizing activity monkeypox virus antibodies B6R-16A1, B6R-21G7, B6R-22D12, B6R-22F9, and B6R-22H1 were obtained. These antibodies have the characteristics of strong binding ability to monkeypox virus, good in vitro neutralization, high affinity, and in vivo protective effect.

The present disclosure provides an anti-human papilloma virus antibody or an antigen-binding fragment thereof. The antibody is derived from memory B cells of vaccinated people, a humanized cross neutralizing antibody capable of neutralizing multiple HPV types is obtained through separation, and the continuous high-concentration neutralizing antibody can neutralize virus particles continuously generated at the vagina mucosa part, prevent viruses from continuously infecting epithelial cells and help an organism to accelerate removal of HPV viruses. And a new scheme is provided for developing antibody drugs for clinical treatment of HPV persistent infection.

The present application relates to monkeypox virus human monoclonal antibody and its application, through screening human antibody humanization mouse anti A29L specific binding memory B cell, the human source high neutralization activity monkeypox virus antibody A29L-1B3, A29L-1B2, A29L-1A5 and A29L-1A2 obtained, have the characteristics such as strong monkeypox virus binding ability, good in-vitro neutralization, affinity, have in-vivo protective effect, and are completely different from the monkeypox virus antibody sequence reported, provide the product for the detection and neutralization of monkeypox virus, and provide the possibility for providing the monkeypox virus product with in-vivo protective effect.

In some embodiments, B cell proliferation and / or memory B cell formation / proliferation may be enhanced by contacting MAIT cells with Noogatointerleukin alpha due to chibercept (N-803) to produce stimulated MAIT cells, which in turn stimulate B cell proliferation and / or memory B cell formation / proliferation. Such stimulation may be performed in the presence of an antigen or antigen presenting cell. In particularly contemplated embodiments, MAIT cell stimulation is performed in vitro to produce an immunostimulatory composition and vaccine, or in vivo to enhance an immune response in airway tissue. Most typically, in vivo immune stimulation is carried out by inhalation or intranasal delivery of a composition comprising N-803 and optionally a vaccine component.

The invention relates to the technical field of biological medicines, in particular to an anti-human helicobacter pylori fully-humanized monoclonal antibody as well as a preparation method and application thereof. The monoclonal antibody comprises one or more of a 4H1-A + 4 lambda 1-25 antibody, a 4H1-A + 4 lambda 1-6 antibody and a 4H1-A + 4 lambda 1-21 antibody; wherein the 4H1-A + 4 lambda 1-25 antibody comprises a 4H1-A heavy chain variable region and a 4 lambda 1-25 light chain variable region; the 4H1-A + 4 lambda 1-6 antibody comprises a 4H1-A heavy chain variable region and a 4 lambda 1-6 light chain variable region; the 4H1-A + 4 lambda 1-21 antibody comprises a 4H1-A heavy chain variable region and a 4 lambda 1-21 light chain variable region. According to the invention, the high-affinity human helicobacter pylori infection-resistant full-human monoclonal antibody is screened through a specific screening method after in-vitro activation of human memory B cells in a laboratory, and an important basis is provided for detection, neutralization and treatment of human helicobacter pylori.

The invention relates to an anti-adalimumab nano antibody and application thereof, an Adalimumab F (ab ') fragment is used as an antigen to immunize alpaca, and the nano antibody is obtained by screening in a memory B cell culture mode; the amino acid sequences of the complementary determining regions CDR1, CDR2 and CDR3 of the nano antibody are respectively as shown in SEQ ID No. 1 to SEQ ID No. 3, or the amino acid sequences of the complementary determining regions CDR1, CDR2 and CDR3 of the nano antibody are respectively as shown in SEQ ID No. 4 to SEQ ID No. 6. The nano antibody has strong adalimumab binding capacity and high specificity, greatly improves the detection sensitivity and accuracy, can be used for drug monitoring, drug resistance research and drug interaction analysis, can be expanded to biological preparation quality control, clinical diagnosis and scientific research tools, and has wide application prospects.

The invention relates to the technical field of immunodetection, and discloses a PLA2R antigen epitope peptide for membranous nephropathy and application thereof. The antigen epitope is selected from at least one of Ricin, CTLD1, CTLD7 and CTLD8. The PLA2R antigen epitope of membranous nephropathy can be combined with a self-reaction B cell and is presented to a T helper cell through a major histocompatibility complex (MHC) II type receptor, the stimulated T cell releases cytokines and feeds back the cytokines to the B cell to stimulate division and differentiation of plasma cells and generate an antibody and memory B cells, and a physiological target of immune response of membranous nephropathy is formed. The important value is realized on the diagnosis and prognosis of membranous nephropathy.

Compositions and methods are provided for determining the presence of early-stage osteoarthritis (OA) in an individual by single cell profiling of B cell population(s) in a blood sample. Expansion of CD25hi switched memory B cells is detectable in the early stages of OA and can be utilized for early detection of the disease.

Provided are a group of fully human thyrotropin receptor (TSHR) (TSH receptor, TSHR) blocking monoclonal antibodies belonging to a SH1 homocluster, a preparation method therefor, and a use thereof. The method comprises the following steps: using flow cytometry to sort plasma cells and individual memory B cells, which specifically recognize TSHR, from peripheral blood of a patient having a high TSH receptor blocking antibody (TBAb) titer, cloning antibody light and heavy chains in vitro, followed by recombinant expression, and performing antibody characteristic screening and verification by using hTSHR-CHO cells, thereby obtaining blocking monoclonal antibodies that specifically target human TSHR. The fully human TSH receptor blocking monoclonal antibodies can specifically bind to TSHR, thereby enabling effective blockage of signal transduction after TSH binds to the receptor, inhibiting the synthesis and secretion of thyroid hormones, and significantly reducing and suppressing the expression of TSHR and fibrosis in orbital fibroblasts, the effector cells in thyroid-related eye diseases. The present invention has broad application prospects in the treatment of Graves' diseases and diseases caused by hyperthyroidism, such as thyroid eye diseases.

The invention is applicable to the technical field of biology, and provides a method for screening a rabbit new crown neutralizing antibody based on a Beacon single cell screening platform, which comprises the following steps: coupling a novel coronavirus antigen protein with a detection microbead; immunizing a rabbit with the antigen protein, and separating peripheral blood mononuclear cells of the rabbit with the titer reaching the standard; enriching memory B cells from the PBMC and activating the memory B cells into plasma cells in vitro; loading the activated cells to a Beacon single-cell antibody screening platform, and carrying out single-cell sorting and multiple rounds of antigen specific screening; unicells which are all positive in multiple rounds of screening are exported, and antibody gene amplification is carried out; according to the present invention, the rabbit new crown neutralizing antibody can be screened with high throughput and high sensitivity by using the Beacon single-cell antibody screening platform so as to significantly improve the antibody screening efficiency; natural pairing of the antibody can be retained, and a high-affinity neutralizing antibody is obtained; the method is simple and rapid to operate, easy to standardize and wide in application prospect.

The present application relates to monkeypox virus human monoclonal antibody and its application, through screening human antibody humanization mouse anti E8L specific binding memory B cell, the human source high neutralization activity monkeypox virus antibody E8L-7H4, E8L-7H2, E8L-7E7, E8L-8D6 and E8L-7C9 obtained, with the characteristics of strong monkeypox virus binding capacity, good in vitro neutralization, affinity, with in vivo protection, completely different from the reported monkeypox virus antibody sequence, provide the product for the detection and neutralization of monkeypox virus, provide the possibility for the monkeypox virus product with in vivo protection.

The invention relates to the field of immunology, in particular to preparation of a mucous membrane adjuvant for recruiting pre-DC and application of the mucous membrane adjuvant in influenza vaccines. Tridecafluoroheptyl ethylene oxide and mannose are grafted on polyethyleneimine, the polyethyleneimine and structural protein hemagglutinin of influenza viruses are adsorbed to form a nano vaccine MF25PEI / HA, secretion of CCL2 is promoted by activating a TLR4 pathway of nasal cavity cDC, pre-DC is recruited and differentiated into cDC, and the network steady state of the nasal cavity cDC is maintained. HA uptake is increased by targeting cDC, cDC maturation is stimulated, and high-level immune response is induced. After intranasal immunization of MF25PEI / HA, secretion of high-level IgA and IgG is caused, activation of B cells, T cells and Tfh cells is promoted, and differentiation of memory B cells and memory T cells is induced. Effective protection can be provided for the influenza H1N1 virus, and a new thought is provided for research and development of respiratory mucosa vaccines.

The invention relates to the field of breast cancer treatment, in particular to a PDIA3 protein targeting monoclonal antibody and application of the PDIA3 protein targeting monoclonal antibody in breast cancer treatment. According to the present invention, the IgG antibody in tumors, lymph nodes and serum is detected by using the IP-MS technology, the breast cancer tumor antigen disulfide isomerase A3 (PDIA3) is screened by analyzing the characteristics of the IgG antibody, and it is proved that the PDIA3 antigen can induce the breast cancer mouse model to produce the local humoral immune response. Meanwhile, it is found that a PDIA3 specific monoclonal antibody based on memory B cell reconstruction in TLN shows potent immune effect activity, wherein an Ab88 antibody can mediate an ADCC / ADCP effect and inhibit tumor growth. In conclusion, the invention provides the local targeting antigen PDIA3 protein with antibody therapy transformation potential and the specific antibody Ab88 thereof, and a new choice is provided for accurate treatment of breast cancer.

The present invention relates to compositions and methods for therapeutic immunization for the treatment of chronic hepatitis B (CHB). The methods of the present invention include methods for producing high titer hybrid hepatitis B virus (HBV) vectors, methods for treating and / or preventing HBV infection and / or CHB, and methods for inducing memory T cell and memory B cell immune responses against HBV infection in subjects administered the VLV compositions produced thereby. Additionally, the present invention includes pharmaceutical compositions for vaccinating a subject to protect the subject against infection by HBV.

This application discloses a human monoclonal antibody against Hennipa virus and its preparation and application as a bispecific antibody. By screening memory B cells in fully human antibody-transgenic mice that specifically bind to Nipah virus glycoproteins (G and F proteins), human monoclonal antibodies 14B8 (targeting the F protein) and 4B8 (targeting the G protein) were obtained. Simultaneously, a bispecific antibody 14B8-IgG-4B8-scFv was constructed based on the above antibodies, which is formed by fusing the full antibody (IgG) of 14B8 with a single-chain antibody fragment of 4B8. Experiments demonstrated that the above antibodies exhibit extremely high binding affinity and neutralizing activity against NiV and HeV, and provide excellent in vivo protective efficacy in the LVG Golden Hamster model.