Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci

Infections with Streptococcus pneumoniae remain a significant cause of morb idity and mortality, To gain insight into structure-function relationships for human antibodies to pneumococcal capsular polysaccharide (PPS)I we stud ied the response of transgenic mice reconstituted with human immunoglobulin loci, XenoMouse, to PPS antigens in a pneumococcal vaccina Enzyme-linked i mmunosorbent assays of sera from mice vaccinated with a 23-valent pneumococ cal vaccine revealed that they produced serotype-specific human antibodies, with the greatest response being to the PPS of serotype 3 (PPS 3, Molecula r sequence analysis of three monoclonal antibodies Ts) to PPS 3 generated f rom lymphoid cells from mite vaccinated with a 23-valent pneumococcal vacci ne or a PPS 3-bovine serum albumin conjugate revealed that they all used he avy-chain immunoglobulin genes from the V(H)3 family, two expressed light c hain genes from the human V kappa 1 family, and one expressed a mouse lambd a light chain. The protective efficacy of the two MAbs was examined in mice . A 10-mu g dose of both, and a 1-mu g dose of one, significantly prolonged survival from a lethal serotype 3 infection in CBA/N mire, Our data show t hat XenoMouse mice produced protective, serotype-specific human antibodies to PPS 3, and they tend support to the proposal that these animals represen t a useful model to study the human antibody response to PPS antigens.