Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain comprising three complementarity determining regions (CDR1-CDR3) and four framework regions, wherein: (a) at least one lysine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue, and/or (b) at least one arginine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue; wherein the polypeptide has increased intestinal stability relative to a corresponding polypeptide not having said histidine substitutions.

The present specification discloses SNAP-25 compositions, methods of making α-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the P.sub.1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, α-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the P.sub.1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, methods of detecting BoNT/A activity, and methods of detecting neutralizing α-BoNT/A antibodies.

A brain-penetrating composition of amyloid-ß binding peptide is disclosed. This may be useful in the treatment of Alzheimer's disease, for example as a bifunctional molecule, comprising a blood-brain barrier crossing antibody and an amyloid-ß targeting peptide linked via an Fc fragment that is able to transmigrate across the blood-brain barrier into the brain, and compositions comprising same. Methods of using this composition for treating Alzheimer's disease are disclosed.

In one aspect, the invention relates to an immunogenic composition that includes a Clostridium difficile toxoid A and/or a C. difficile toxoid B, and methods of use thereof. In another aspect, the invention relates to a method for eliciting an immune response in a human against a C. difficile infection. The method includes administering to the human an effective dose of a composition, which includes a C. difficile toxoid, wherein the composition is administered at least two times, and wherein the immune response against C. difficile toxin A and/or toxin B is sustained.

In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins. The antibodies and derivatives thereof that specifically bind to the neutralizing epitopes provided herein can be used in methods to specifically bind and, in some embodiments, neutralize, botulinum neurotoxin and are therefore also useful in the treatment.

The present invention relates to the use of plasma immunoglobulin, such as intramuscular immunoglobulin, in combination with polyclonal antigen-specific immunoglobulin in the treatment or prevention of autoimmune diseases. The invention furthermore relates to a pharmaceutical composition for the treatment or prevention of autoimmune diseases comprised of plasma immunoglobulin in combination with polyclonal antigen-specific immunoglobulin.

The present invention pertains to a vaccine comprising (a) an immunologically effective amount of a Streptococcus suis IgM protease antigen, (b) an immunologically effective amount of an Escherichia coli fibmrial antigen, and (c) an immunologically effective amount of a Clostridium toxoid, and also pertains to use of the vaccine in a method for protecting pigs against a pathogenic infection with Streptococcus suis, Escherichia coli and Clostridium.

Embodiments of the present invention provide methods for the treatment or prevention of infection-related immune conditions using compositions comprising IgM.