Nd. Russell et al., Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci, INFEC IMMUN, 68(4), 2000, pp. 1820-1826
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.