CONTEXT: The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. OBJECTIVE: To determine the safety and immunogenicity of a combination 9-valent pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. DESIGN, SETTING, AND PARTICIPANTS: Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. INTERVENTION: Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). MAIN OUTCOME MEASURES: Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. RESULTS:MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] microg/mL vs 3.36 [95% CI, 2.57-4.39] microg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] microg/mL vs 1.47 [95% CI, 1.28-1.69] microg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 microg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. CONCLUSIONS:Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.
RCT Entities:
CONTEXT: The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. OBJECTIVE: To determine the safety and immunogenicity of a combination 9-valent pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. DESIGN, SETTING, AND PARTICIPANTS: Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. INTERVENTION: Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). MAIN OUTCOME MEASURES: Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. RESULTS: MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] microg/mL vs 3.36 [95% CI, 2.57-4.39] microg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] microg/mL vs 1.47 [95% CI, 1.28-1.69] microg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 microg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. CONCLUSIONS: Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.
Authors: Michael P Broderick; Sandra Romero-Steiner; Gowrisankar Rajam; Scott E Johnson; Andrea Milton; Ellie Kim; Lisa J Choi; Jennifer M Radin; Daniel S Schmidt; George M Carlone; Nancy Messonnier; Dennis J Faix Journal: Clin Vaccine Immunol Date: 2016-08-05
Authors: Nik G Johnson; Jens U Ruggeberg; Gail F Balfour; Y Chen Lee; Helen Liddy; Diane Irving; Joanna Sheldon; Mary P E Slack; Andrew J Pollard; Paul T Heath Journal: Emerg Infect Dis Date: 2006-06 Impact factor: 6.883