Recombinant polyclonal proteins and methods of use thereof

A pharmaceutical composition comprising a library of recombinant polyclonal proteins (RPPs), wherein the library comprises at least 100 RPPs specifically binding to an antigen and has been generated by the process of:

• a. isolating single cells from a spleen, lymph node, or peripheral blood sample from a donor exposed to the antigen, wherein the single cells are CD43+ plasmablasts, CD27+ memory B cells, or peripheral CD138+ plasma cells;
• b. amplifying polynucleotides, wherein each of the polynucleotides encodes a cognate pair of heavy chain and light chain variable regions from one of the single cells by overlap extension reverse transcriptase polymerase chain reaction (OE-RT-PCR);
• c. cloning the polynucleotides obtained from the amplification into an expression vector, thereby obtaining the constructs encoding antibody fragments;
• d. generating antibody expression constructs using the constructs or a subset of the constructs, wherein each of the antibody expression constructs encodes a light chain variable region, a kappa or lambda-type light chain constant region, a heavy chain variable region, and a heavy chain constant region,
• e. introducing the antibody expression constructs into a cell line, and
• f. expressing antibodies from the antibody expression constructs in the cell line, thereby obtaining the at least 100 recombinant polyclonal proteins (RPPs);
• wherein each of the RPP is an antibody comprising a cognate pair of heavy chain and light chain variable regions from a single cell out of the sample.