Infectious Diseases in Children
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IMay 2005 Issue
Breaking News & Commentary
Meningococcal combo vaccine not successful in U.K. infants2
Pnc9-MenC did not provide adequate immunity against serogroup C
meningococcal disease.
A combination vaccine developed to reduce the number of vaccines infants
receive appears to provide less immunity than the vaccines administered
individually, according to a study in the Journal of the American Medical
Association (JAMA). Vol. 293 No. 14, April 13, 2005.
The researchers concluded, "These results highlight the unpredictability of
immune responses to individual vaccine antigens after incorporating multiple
antigens into combination vaccines and underline the importance of assessing
the immunogenicity of all coadministered vaccine antigens in prelicensure
trials. The Pnc9-MenC vaccine as tested may not be a suitable replacement
for individual MenC or pneumococcal glycoconjugate vaccine."
Jim P. Buttery, FRACP, formerly of the University of Oxford, Churchill
Hospital, Headington, Oxford, U.K., and colleagues, conducted a study to
determine the immunogenicity and safety of a combination nine-valent
pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC).
The phase 2 randomized controlled trial was conducted from August 2000 to
January 2002 and enrolled 240 healthy infants ages 7 to 11 weeks from two
centers in the United Kingdom, with home follow-up visits at ages 2, 3, 4,
and 5 months.
Individual vaccine proves better
Infants received 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).
The researchers concluded "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 researchers concluded that, "These results highlight the
unpredictability of immune responses to individual vaccine antigens after
incorporating multiple antigens into combination vaccines and underline the
importance of assessing the immunogenicity of all coadministered vaccine
antigens in prelicensure trials. The Pnc9-MenC vaccine as tested may not be
a suitable replacement for individual MenC or pneumococcal glycoconjugate
vaccines."
Combo vaccines
Since the introduction of a MenC vaccine into routine immunization schedule
in the United Kingdom in November 1999, group C meningococcal disease has
decreased by 87% in the ages targeted for vaccination, with estimated
vaccine efficacy of 90%, according to a JAMA press release.
Within two years of the introduction of a seven-valent pneumococcal
glycoconjugate vaccine (PCV7, Prevnar, Wyeth) into the recommended infant
schedule in the United States, there was a 69% reduction in culture-positive
invasive pneumococcal disease in children younger than age 2.
The advent of these vaccines has increased pressure on crowded infant
immunization schedules. Infants in the United States receive up to 20
separate vaccine injections over five immunization encounters at ages 2, 4,
6, 12, and 18 months to protect against disease.
The combining of pneumococcal and meningococcal conjugate vaccines has the
potential to spare U.S. infants up to four extra injections by age 18 months
and to decrease parental and clinician concerns about the number of
vaccinations.
For more information:
Buttery JP, Riddell A, McVernon J, et al. Immunogenicity and safety of a
combination pneumococcal-meningococcal vaccine in infants. JAMA.
2005:293(14);1751-1758.
JAMA
Vol. 293 No. 14, April 13, 2005
ABSTRACT
Immunogenicity and Safety of a Combination Pneumococcal-Meningococcal
Vaccine in Infants
A Randomized Controlled Trial
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] �g/mL vs 3.36 [95% CI, 2.57-4.39]
�g/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI,
0.63-0.87] �g/mL vs 1.47 [95% CI, 1.28-1.69] �g/mL; P<.001). Pnc9-MenC was
immunogenic for each of 9 contained pneumococcal serotypes, with responses
greater than 0.35 �g/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.
