An investigational vaccine against meningococcal B disease produced robust immune responses in infants, researchers reported.
In a randomized, open-label trial, the multi-component 4CMenB vaccine was immunogenic and had minimal interference when administered with routine childhood shots, according to Matthew Snape, MD, FRCPCH, of Oxford University in the U.K., and colleagues.
On the other hand, while there were few serious adverse events, fever was common after 4CMenB shots, ranging from 71% to 80%, Snape and colleagues reported in the Feb. 8 issue of the Journal of the American Medical Association.
Disease caused by serotypes A, C, W-135, and Y of Neisseria meningitidis can be combated by capsular polysaccharide vaccines, but the corresponding proteins of the B serotype are too similar to a human protein to be immunogenic, the researchers noted.
The lack of a vaccine means meningococcal B disease can be devastating, commented Amanda Cohn, MD, and Nancy Messonnier, MD, both of the Centers for Disease Control in Atlanta.
In an accompanying editorial, they noted that meningococcal B disease is fatal in up to 10% of young victims, and between 10% and 20% experienced long-term effects, including hearing loss and neurologic deficits.
The results of this study are a "major step forward" in making a broadly protective vaccine, they said, but cautioned that questions remain, including issues regarding the need for boosters, the likelihood of producing herd immunity, and costs versus benefits.
Because the polysaccharide approach was not possible for this serogroup, Snape and colleagues noted, the 4CMenB vaccine contains outer membrane proteins from a recent epidemic strain, combined with three surface-expressed proteins identified by sequencing the genome of the bacterium:
- Factor-H binding protein variant 1(fHbp1)
- Neisserial adhesin A (NadA)
- Neisseria heparin binding antigen (NHBA)
In smaller studies in infants, the vaccine has been shown to be immunogenic. As well, a recent study in adolescents found a robust immune response.
The goal of the current study was to examine the immunogenicity and reactogenicity of 4CMenB and routine infant vaccines given either together or separately.
More than 1,800, 2-month-old infants were randomly assigned to four immunization groups. The first group, the control, received routine vaccines alone (seven-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b) at ages 2, 3, and 4 months.
The other three groups were:
- A group given three doses of 4CMenB and the routine vaccines together at ages 2, 4, and 6 months
- A group given 4CMenB with routine shots together on an accelerated schedule at ages 2, 3, and 4 months
- Infants given 4CMenB at ages 2, 4, and 6 months and the routine shots intercalated at ages 3, 5, and 7 months
For the primary outcome, the researchers measured immune response with the human serum bactericidal antibody assay, in which a concentration of 1:5 or greater correlates with protection. They found that after immunization with 4CMenB and routine vaccines together in either schedule, immune response to two of the three proteins was 99% or higher, and was between 79% and 86.1% for the third protein.
The responses to routine shots given with 4CMenB were noninferior to routine vaccines alone for all but two of the antigens involved. The exceptions were pertactin (a pertussis antigen) and the pneumococcal vaccine serotype 6B.
Fever (≥38°C) was seen in 26% to 41% of the 4CMenB doses when administered alone to the infants versus 23% to 36% of routine vaccines doses given alone and 51% to 61% of 4CMenB and routine vaccine doses given together.
Fever after any vaccination was seen in between 76% and 80% of children who received 4CMenB and routine shots together compared with 51% in the control group and 71% in the group whose vaccinations were intercalated.
Developing a broadly protective vaccine against meningococcal B disease has been "a formidable challenge and, if successful, would represent an enormous step forward in the prevention of childhood meningitis," Snape said in a statement. The vaccine appears to be usable in a variety of immunization schedules, he and his colleagues said.
But the high fever rates imply that there is "a need to compare the risk profile of a relatively common, but transient, post-immunization fever with the benefit of reducing the risk of an uncommon, but potentially fatal, meningococcal infection," they cautioned.
They added that the open-label design of the study could have allowed a bias to creep into the adverse event profile, if parents of children given the vaccine were more alert to side effects.
The study was funded by Novartis Vaccines and Diagnostics. Snape and other authors reported financial links with some or all of Novartis Vaccines, GlaxoSmithKline, sanofi-aventis, Sanofi Pasteur MSD, MedImmune, and Pfizer Vaccines.
The editorial authors did not report any potential conflicts.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Journal of the American Medical AssociationSource Reference: Gossger N, et al "Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial" JAMA 2012; 307: 573-582.
Journal of the American Medical AssociationSource Reference: Cohn AC, Messonnier NE "Inching toward a serogroup B meningococcal vaccine for infants" JAMA 2012; 307: 614-615.