The present invention relates to methods and compositions for use in modulating, including inhibiting the growth and/or reducing the virulence of, gram-positive bacteria. The present invention provides methods and compositions for disrupting the cell wall and/or cell membrane in gram-positive bacteria such that cell wall or cell membrane target(s) are rendered exposed or accessible and sensitive to a modulation thereof. Methods for modulation of one or more gram-positive bacterial cell wall or cell membrane targets in a gram-positive bacteria are provided comprising disrupting the cell wall such that the cell wall or cell membrane target, which is particularly a sortase, is rendered exposed or accessible and sensitive to a modifying, modulating or binding agent, which is particularly an antibody or fragment thereof, wherein the cell wall or cell membrane target is inaccessible or relatively insensitive to the modifying, modulating or binding agent in the absence of cell wall disruption.

The present invention relates to peptides, particularly human monoclonal antibodies, that bind specifically to poly-N-acetyl glucosamine (PNAG), such as Staphylococcal PNAG, in acetylated, partially acetylated and/or fully deacetylated form. The invention further provides methods for using these peptides in the diagnosis, prophylaxis and therapy of infections by bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Some antibodies of the invention enhance opsonophagocytic killing and in vivo protection against bacteria that express PNAG such as but not limited to Staphylococci and E. coli. Compositions of these peptides, including pharmaceutical compositions, are also provided, as are functionally equivalent variants of such peptides.

Anti-SpA murine, chimeric and humanized monoclonal antibodies, and variant antibodies having a heavy chain with at least one amino acid substitution are provided. Such antibodies may be used to prevent or treat microbial infections.

A human immunoglobulin against Methicillin-resistant Staphylococcus aureus, and human immunoglobulin against Methicillin-resistant Staphylococcus aureus is prepared by collecting plasma of a healthy plasma donor immunized with Methicillin-resistant Staphylococcus aureus vaccine, wherein the Staphylococcus aureus vaccine has a valence of antigen mHla of no less than 1:3,200, valence of antigen IsdB of no less than 1:1,600, valence of antigen MntC of no less than 1:1,600, valence of antigen mSEB of no less than 1:6,400, and valence of antigen SpA5 of no less than 1:400, and total content of IgG monomers and dimers is over 90.0%. The human immunoglobulin against Methicillin-resistant Staphylococcus aureus has high valence and high purity, which can not only have good effects for preventing and treating Methicillin-resistant Staphylococcus aureus infection, but also avoid a problem of drug resistance caused by antibiotic treatment, and has important clinical significance and broad market prospects.

The present invention relates to methods for treating and preventing Staphylococcus aureus infection and/or a condition resulting from a S. aureus infection in a subject that involves administering compositions that inhibit S. aureus interaction with CXCR1/CXCR2 and DARC cellular receptors. The present invention further relates to novel compositions for carrying out these and other methods.

Provided by the present disclosure are antibodies (e.g., scFvs) that include CDRs and human framework regions that confer useful properties upon the antibodies. In certain embodiments, such properties include thermostability (e.g., increased melting temperature), efficient binding to Staphylococcus aureus Protein A, or both. In certain aspects, the antibodies are internalizing antibodies that specifically bind to the tumor associated antigen EphA2.

[Problem] The present invention addresses the problem of providing an anti-Staphylococcus antibody having preventive or therapeutic effects on staphylococcal infections. [Solution] Provided is an anti-Staphylococcus antibody having preventive or therapeutic effects on staphylococcal infections and a method for manufacturing said antibody, as well as a composition, a product, and a drug containing said antibody. The antibody is obtained by using deacetylated Staphylococcus for immunization.

Binding agents able to disrupt bacterial biofilms of diverse origin are described, including monoclonal antibodies secreted by human B lymphocytes. Methods to prevent formation of or to dissolve biofilms with these binding agents are also described. Immunogens for eliciting antibodies to disrupt biofilms are also described.

Processes are described for the preparation of F-benzoxazinorifamycin I:

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and intermediates for conjugation with an antibody.

Provided herein are methods of treating a COVID-19 infection in a subject, comprising administering to the subject an effective amount of a composition that reduces the superantigen character of SARS-CoV-2 Spike protein. In some embodiments, the compositions are mimetic peptides of the superantigen region. In some embodiments, the compositions are humanized antibodies, such as humanized mAb 6D3, that bind to the superantigen region.