Meningitis B Vaccine Booster May Prolong Protection in Kids

Troy Brown, RN

September 23, 2013

Giving a booster of a new meningitis B vaccine at 40 months of age to children who received it at 2, 4, 6, and 12 months appears to overcome waning immunity that is common with meningitis vaccines, according to a study published online September 23 in the Canadian Medical Association Journal.

The multicomponent serogroup B meningococcal vaccine (4CMenB) was recently licensed for use in Europe and is under consideration for use in Canada. However, the persistence of immunity into childhood remains unclear.

Therefore, Matthew D. Snape, MBBS, MD, a consultant in vaccinology and general pediatrics in the Department of Paediatrics at Oxford Biomedical Research Centre in the United Kingdom, and colleagues measured serogroup B–specific bactericidal antibodies in children aged 40 to 44 months who had received 4 doses of the vaccine as infants.

The 4CMenB vaccine is made of 3 recombinant proteins: factor H binding protein (fHbp), Neisseria adhesin A (NadA), and Neisseria heparin binding antigen (NHBA), combined with detoxified outer membrane vesicles from the strain that caused an epidemic of serogroup B meningococcal disease in New Zealand.

The researchers compared the vaccine responses in children who had participated in a previous trial and vaccine-naive, age-matched control participants. The treatment group included children aged 40 to 44 months who had received 1 of 4 vaccine regimens: the 4CMenB vaccine or a vaccine containing the recombinant proteins alone (recombinant protein serogroup B meningococcal [rMenB] vaccine) at 2, 4, 6, and 12 months of age; 4CMenB at 12 months; or rMenB at 12 months.

Of the 125 children enrolled in the first study 68 enrolled in the follow-up study. In addition, 40 MenB vaccine-naive, age-matched participants enrolled in the follow-up study.

Children who received 4 doses in infancy received a single booster shot, whereas those who received a single dose in infancy received 2 booster shots. Unvaccinated control participants received 2 booster shots at ages 42 and 44 months.

The investigators measured human complement serum bactericidal activity (hSBA) titers from serum samples obtained at baseline and 1 month after each dose of 4CMenB.

Before the children received a booster dose at enrollment, 41% to 76% of 17 children previously vaccinated with 4CMenB in infancy had hSBA titers of 1:4 or greater against 4 reference strains.

At baseline, of those who received 4CMenB at 12 months, 25% had hSBA titers of at least 1:4 for strains M10713 (NHBA), and 38% had hSBA titers of at least 1:4 for strain 44/76-SL (9fHbp). These proportions were 0% for strains 5/99 (NadA) and NZ98/254 (PorA).

Before the children in the control group were vaccinated, similar proportions were found for strains 44/76-SL (63%) and M10713 (68%) and for strains NZ98/254 (0%) and 5/99 (3%).

After the booster dose of 4CMenB, 86% to 100% of 4CMenB-primed participants achieved hSBA titers of 1:4 or greater for all strains except M01-240355. The 4CMenB-primed children experienced greater increases in hSBA titers after the booster dose than those in the control group.

After vaccination in early infancy with either vaccine, antibodies had waned at baseline. At least 65% of those given 4CMenB at 2, 4, 6, and 12 months had hSBA titers of at least 1:4 at baseline for strains 44/76-SL (evaluating fHbp), 5/99 (NadA), and M10713 (NHBA) compared with 41% for NZ98/254 (PorA). Among those given rMenB at 2, 4, 6, and 12 months of age, 43% or more had hSBA titers of 1:4 or greater for these strains, with the exception of NZ98/254 (PorA) (3%).

Regardless of the vaccine given, the percentage of children with hSBA titers of at least 1:4 for strain M01-24-355 was low.

Administration of the 4CMenB 2 months apart to MenB vaccine-naive children caused 89% to 100% of the children to achieve hSBA titers of at least 1:4 for all strains except M01-240355 (69%), and more than 50% of the participants had hSBA titers greater than 1:4 for strains 44/76-SL (fHbp), M10713 (NHBA), M01-240101, and M01-240364 at baseline, and hSBA geometric mean titers were similar to those of children who were given 4CMenB at 2, 4, 6, and 12 months.

For children who received a 4CMenB booster, the geometric rise in hSBA titers for all strains was higher in those who received 4CMenB at 2, 4, 6, and 12 months than in the control participants.

David Hyun, MD, a pediatric infectious disease specialist at Children's National Medical Center in Washington, DC, commented on the study in an email interview with Medscape Medical News.

"My understanding is that it's only licensed in Europe at this time. So in reality there wouldn't be any clinical impact for children in the US from this study. There's also a considerable amount of debate among United States experts on whether infants should be vaccinated against any meningococcal types," Dr. Hyun said.

Novartis Vaccines and Diagnostics funded this study, including providing the study vaccine, performing laboratory analysis of the sera, and developing this protocol in collaboration with 3 of the authors. The research was supported by the National Institute for Health Research Oxford Biomedical Research Centre based at Oxford University Hospitals National Health Service Trust and University of Oxford. Dr. Snape and 1 coauthor have conducted clinical trials on behalf of the University of Oxford, sponsored by Novartis Vaccines and Diagnostics, Pfizer, GlaxoSmithKline, and Sanofi-Pasteur MSD but do not receive personal payments from vaccine manufacturers; grants for support of educational activities are paid to an educational/administrative fund held by the Department of Paediatrics, University of Oxford. Dr. Snape and 1 coauthor have received assistance to attend scientific meetings from Novartis, Pfizer, and GlaxoSmithKline. Dr. Snape and 1 coauthor are supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Snape has spent a period of secondment at Novartis. One coauthor chairs the European Medicines Agency’s Scientific Advisory Group on Vaccines, is a member of the UK Department of Health’s Joint Committee on Vaccination and Immunisation Meningococcal Sub-committee, and is a Jenner Institute investigator and a James Martin senior fellow. Three coauthors are employees of Novartis Vaccines and Diagnostics. The other authors and Dr. Hyun have disclosed no relevant financial relationships.

CMAJ. Published online September 23, 2013. Full text


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