PNEUMOCOCCAL VACCINE PREVENT NASOPHARYNGEAL COLONIZATION--INFANT RHESUS MONKEY

SPID # 17

SPID# 17 This study had three main objectives (1) To develop and evaluate a rhesus monkey (Macaca mulatta) model for nasopharyngeal colonization of Streptococcus pneumoniae. (2) To evaluate various vaccine candidates for human use in infant monkeys to test the hypothesis that a successful parenteral immunization prevents or decreases pneumococcal nasopharyngeal carriage. (3) To correlate the humoral immune responses to pneumococcal vaccine with the mucosal (salivary) responses. During this reporting period, sixteen infant rhesus monkeys (4 groups of 4) were immunized IM at 2, 4, and 6 mo of age with a heptavalent pneumococcal conjugate vaccine (Lederle-Praxis) with adjuvants (either alum alone, alum+MPL, or alum+QS-21); the control group was not immunized. IgG serum antibodies to serogroups 4, 6B, 9V, 14, 18C, 19F, and 23F were measured (pre, post 2, 4, and 7 mo) by ELISA (fg/ml). The vaccine was immunogenic (Table 1) with each of the three adjuvants; alum alone gave the lowest antibody concentrations for all serotypes, alum+MPL gave the highest for serotypes 6B, 9V, and 14, and alum+QS-21 gave the highest for serotypes 4, 18C, 19F, and 23F. Table 1. IgG(GM) for serotypes measured by ELISA (1 mo post dose 3) Serogroups Group 4 6B 9V 14 18C 19F 23F Control 0.16 0.31 0.14 0.30 0.05 0.45 0.12 Alum alone 13.9 28.7 21.8 14.7 11.2 53.6 17.5 Alum+MPL 27.1 89.2 57.5 43.2 19.0 71.8 28.3 Alum+QS-21 31.0 64.0 44.8 25.4 31.9 112.3 50.6 Opsonophagocytic titers (Table 2) were measured using HL-60 cells. Table 2. Opsonophagocytic titers (GM) for serotypes 14 and 18C Serotype 14 Serotype 18C Group pre post1 post2 post3 pre post1 post2 post3 Control 4 4 4 4 4 4 4 4 Alum alone 4 7 19 76 4 16 32 128 Alum+MPL 4 13 45 181 4 19 19 90 Alum+QS-21 4 11 19 76 4 32 128 724 In general, antibody levels were higher with alum+MPL or alum+QS-21 than with alum alone.