A murine model for the study of immune memory in response to pneumococcal conjugate vaccination

Abstract

We developed a murine model for assessment of immunological memory and antibody-induced protection to nasopharyngeal (NP) challenges. BALB/c female mice ( n=10 mice per study parameter) were immunized with two priming doses of the licensed 7-valent pneumococcal (Pnc) conjugate vaccine and immune responses [antibody immunoglobulin G (IgG) levels, avidity and opsonophagocytic activity] were monitored for 26 weeks until IgG levels decreased to nearly baseline. A booster dose of either 2 μg conjugate or 5 μg polysaccharide vaccine was given at week 26. The ability of these two treatments to recall immune memory established by the conjugate vaccine was determined for types 4 and 14 for up to 63 days post-booster. The ability of challenge with pneumococcal type 14 to recall the immune response was also evaluated, as well as, the number of antibody secreting cells (ASC) specific to polysaccharide (Ps) 4, 6B, and 14. A higher dose of conjugate vaccine (2 μg) was necessary to elicit a significant increase in IgG levels after priming with one dose. Priming with lower doses (0.5 and 1.0 μg) only elicited modest increases in IgG levels. Recall of the immune response was found with either conjugate or Ps vaccines. NP challenge with type 14 at week 26 did not recall the immune response, although reduction in NP Pnc load was seen post-primary immunization at 5, 10 and 26 weeks. ASCs were detected in response to either conjugate or Ps booster doses. This model allows for the screening and determination of potential alternative vaccination regimens and the study of immunological markers of memory following Pnc vaccination.