SCID-Hu mice immunized with a pneumococcal vaccine produce specific human antibodies and show increased resistance to infection.
Seventy-eight severe combined immunodeficiency (SCID) mice were administered intraperitoneally 1 x 10(7) to 9 x 10(7) human peripheral blood mononuclear cells (PBL) in five experiments. Human immunoglobulin G (IgG) was detected in 70 to 88% of these SCID-PBL-Hu mice after cell transplantation, and all four subclasses were present. The total concentration of human IgG varied from less than 1 to 10.2 g/liter. The SCID-PBL-Hu mice with high concentrations of human IgG regularly had mono- or oligoclonal human IgG bands in serum, as demonstrated by agarose gel electrophoresis. Of the SCID-PBL-Hu mice that were immunized with a 23-valent pneumococcal polysaccharide vaccine, 63 to 78% developed a significant human IgG antipneumococcal antibody response, whereas only very low levels of human IgM and no human IgA antipneumococcal antibodies could be detected. Twelve to twenty-two percent of the SCID-PBL-Hu mice showed signs of leakiness; these mice developed a significant mouse IgM antipneumococcal antibody response and no human antibodies. SCID-PBL-Hu mice were challenged intraperitoneally with 10 50% lethal doses of Streptococcus pneumoniae serotype 4 to study the protective effect of immunization with pneumococcal vaccine. The immunized SCID-PBL-Hu mice showed less bacteremia than did all control groups, and survival was 45 to 60%. None of the unimmunized SCID-PBL-Hu mice survived.
Aaberge
I S
IS
Department of Immunology, National Institute of Public Health, Oslo, Norway.
Michaelsen
T E
TE
Rolstad
A K
AK
Groeng
E C
EC
Solberg
P
P
Løvik
M
M
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D007074:Immunoglobulin G / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D008954:Models, Biological; D022242:Pneumococcal Vaccines; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014183:Transplantation, Heterologous
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines