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Published on: April 14, 2011
Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled
Jim P Buttery1, Anna Riddell, Jodie McVernon
1Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford, UK. jim.buttery@rch.org.au
Insights
A new combination vaccine (Pnc9-MenC) for infants showed reduced immune responses to the group C meningococcal component and other routine vaccines. While safe and immunogenic for pneumococcal serotypes, diminished MenC response may hinder its development.
Area of Science:
- Pediatric infectious diseases
- Vaccine development and immunology
- Public health and immunization policy
Background:
- Rising invasive diseases from Streptococcus pneumoniae and Neisseria meningitidis necessitate combination vaccines.
- Crowded infant immunization schedules drive the need for efficient vaccine combinations.
- Development of conjugate vaccines has been crucial in reducing disease burden.
Purpose of the Study:
- To assess the safety and immunogenicity of a novel 9-valent pneumococcal-group C meningococcal conjugate vaccine (Pnc9-MenC).
- To evaluate Pnc9-MenC when administered within the routine UK infant immunization schedule at 2, 3, and 4 months of age.
- To compare immune responses and adverse events between Pnc9-MenC and a monovalent group C meningococcal vaccine (MenC).
Main Methods:
- Phase 2 randomized controlled trial involving 240 healthy infants aged 7-11 weeks.
- Infants received either Pnc9-MenC (n=120) or MenC (n=120) alongside routine immunizations (DTwP, Hib, polio vaccine).
- Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) one month post-vaccination; safety assessed via adverse event monitoring.
Main Results:
- Pnc9-MenC demonstrated significantly reduced group C meningococcal immunogenicity compared to MenC vaccine (SBT geometric mean 179 vs 808, P<.001).
- Concomitant administration of Pnc9-MenC reduced immunogenicity for Haemophilus influenzae type b (Hib) and diphtheria components of routine vaccines.
- Pnc9-MenC was immunogenic for all 9 pneumococcal serotypes, with >88% infants achieving antibody levels >0.35 microg/mL; increased irritability noted post-vaccination.
Conclusions:
- The Pnc9-MenC combination vaccine showed reduced immunogenicity for the group C meningococcal component and diminished responses to concurrently administered vaccines.
- The vaccine was safe and elicited protective immune responses against the 9 pneumococcal serotypes included.
- The observed reduction in MenC immunogenicity may pose a challenge for the clinical development and licensure of the Pnc9-MenC vaccine.
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.
