Mouse antibody to phosphocholine can protect mice from infection with mouse-virulent human isolates of Streptococcus pneumoniae

Abstract

Previous studies have demonstrated that mouse antibodies to phosphocholine (PC) can protect mice against fatal infection caused by several, but not all, mouse-virulent laboratory strains of Streptococcus pneumoniae. Because the pneumococcal strains used in previous studies had been mouse passed and were propagated for many years outside of humans, it was not known whether antibody to PC would be able to protect mice against S. pneumoniae freshly isolated from humans. In the present study, we examined the ability of an immunoglobulin G (IgG) monoclonal antibody (MAb) to PC to protect against infections in mice caused by 14 pneumococcal strains of capsular types 3, 4, 6A, and 6B. Nine of these strains were selected as the most virulent strains for mice from a group of 69 fresh clinical isolates. Five were mouse-passed laboratory strains. Mouse IgG3 MAb to PC was able to exhibit protective effects (survival or increased time to death) against infection with virtually all of the strains injected intravenously and against infection with 70% of the strains injected intraperitoneally. The protective effects of antibody to PC appeared to be partially dependent on capsular type. MAb to PC was most effective against capsular type 3 strains and least effective against type 4 strains. With type 3 and type 4 strains, MAb to PC could frequently protect against larger numbers of CFU injected intravenously than intraperitoneally. For capsular type 6A and 6B strains the reverse was true.

Effect of genetic switching of capsular type on virulence of Streptococcus pneumoniae

“…Ten-milliliter liquid cultures, grown to an OD600 of -0.5, were harvested by centrifugation for 10 to 15 min at 8,000 to 16,000 x g. Bacteria were washed twice with water prior to being loaded onto 10-ml, continuous, 0 to 50% Percoll (Pharmacia, Piscataway, N.J.) gradients. As standards, 5 ,ul of density marker beads (Pharmacia) ranging in size from 1.033 to 1.076 g/ml, were also loaded. Gradients were centrifuged for 30 min at 8,000 x g with the brake off.…”

“…In a study of 76 S. pneumoniae strains representing eight capsular serotypes or groups, the virulence of the isolates in terms of ability and time required to kill infected mice was strongly associated with the capsule type of the invading strain (4). In addition, the ability to protect against pneumococcal challenge in mice with antibodies to the cell surface components phosphocholine and pneumococcal surface protein A (PspA) differs with the invading strain and may be affected by the capsular serotype (5,25,27,33,40).…”

A pneumolysin-negative mutant of Streptococcus pneumoniae causes chronic bacteremia rather than acute sepsis in mice

“…Infection with type 6B pneumococci results in a chronic infection similar to that of PLN, where the median time of death was about 7 days. This stands in contrast to the much more rapid septic deaths caused by capsular types 2, 3, and 4 pneumococci (10,11). This could be because although PLN preinfection prevents rapid sepsis, it does not affect the course of chronic S. pneumoniae infection.…”

Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A.

“…Mouse Protection Experiments in rBCG-Pst~A Immunized Mice. BALB/c and C3H/HeJ mice immunized with rBCG-PspA vaccine strains were challenged intraperitoneally with 104 CFU (100 x LDs0) of the highly lethal S. pneumoniae strain WU2 (34). Immediately after challenge, samples of the S. Imeumoniae challenge inoculum were plated on trypticase soy blood agar plates to determine the CFU and verify the challenge dose.…”