The present disclosure is directed to leukotoxin-binding antibodies and antigen-binding fragments thereof. The antibodies and fragments can be used, for example, to detect leukotoxin and/or in methods of treating and preventing Staphylococcus aureus infections.

The current disclosure provides novel compositions for treating bacterial infections. Accordingly, aspects of the disclosure relate to an engineered antibody comprising: LCDR1, LCDR2, and LCDR3 of the light chain variable region of the 3F6 antibody and HCDR1, HCDR2, and HCDR3 of the heavy chain variable region of the 3F6 antibody. Also provided are compositions comprising the antibodies and nucleic acids encoding either the heavy chain or light chain (or both) of the antibodies. Other aspects relate to host cells comprising the antibodies and/or nucleic acids of the disclosure. Further aspects relate to a method of preventing or treating staphylococcal infection comprising the step of administering the antibody of the disclosure to a subject in need thereof. Yet further aspects relate to a method of making the antibody comprising expressing the nucleic acid(s) of the disclosure in a cell and isolating the expressed protein.

The present invention concerns a method of storing a separation matrix comprising multimers of immunoglobulin-binding alkali-stabilized Protein A domains covalently coupled to a porous support. The method comprises the steps of: a) providing a storage liquid comprising at least 50% by volume of an aqueous alkali metal hydroxide solution; b) permeating the separation matrix with the storage liquid; and c) storing the storage liquid-permeated separation matrix for a storage time of at least days. The alkali-stabilized Protein A domains comprise mutants of a parental Fc-binding domain of Staphylococcus Protein A (SpA), as defined by, or having at least 80% such as at least 90%, 95% or 98% identity to, SEQ ID NO 51 or SEQ ID NO 52, wherein the amino acid residues at positions 13 and 44 of SEQ ID NO 51 or 52 are asparagines and wherein at least the asparagine residue at position 3 of SEQ ID NO 51 or 52 has been mutated to an amino acid selected from the group consisting of glutamic acid, lysine, tyrosine, threonine, phenylalanine, leucine, isoleucine, tryptophan, methionine, valine, alanine, histidine and arginine.

Hidradenitis suppurativa can be treated by administering a pharmaceutical composition that includes a pharmaceutically acceptable carrier and a therapeutically effective amount of an agent that selectively binds IL-1α.

As described below, the present invention features genetically modified immune cells having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft versus host reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

Herein is reported a polypeptide comprising a first polypeptide and a second polypeptide each comprising in N-terminal to C-terminal direction at least a portion of an immunoglobulin hinge region, which comprises one or more cysteine residues, an immunoglobulin CH2-domain and an immunoglobulin CH3-domain, wherein the first, the second, or the first and the second polypeptide comprise the mutation Y436A (numbering according to the EU index).

The present disclosure relates to an antibody or antigen-binding fragment thereof that specifically bind to α-toxin of Staphylococcal aureus. The present disclosure also relates to a pharmaceutical composition, a method for treating and/or preventing diseases and/or disorders caused by Staphylococcal aureus infection in a subject in need, and a method for detecting α-toxin of Staphylococcal aureus in a sample.

The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy.

Disclosed herein are isolated and purified Staphylococcus aureus bi-component leukocidin, referred to herein as LukAB, and its components LukA and LukB, antibodies specific to LukA, antibodies specific to LukB, therapeutic compositions containing LukA and/or LukB, or anti-LukA and/or anti-LukB antibodies, uses of the compositions to treat acute inflammatory conditions or S. aureus infection, methods for identifying inhibitors of LukAB-mediated cytotoxicity of human phagocytes, and methods for using LukAB as a marker to predict severity of S. aureus infection.

The present invention provides antibodies that bind to Staphylococcus aureus Hemolysin A toxin, and methods of use. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to Hemolysin A. The antibodies of the invention are useful for inhibiting or neutralizing Hemolysin A activity, thus providing a means of preventing or treating a Hemolysin A-related disease or disorder such as S. aureus infection. In some embodiments, the antibodies of the present invention are used in treating at least one symptom or complication of a S. aureus infection.