New vaccine protected adolescents against meningococcal B

A two-dose regimen of a multicomponent meningococcal serogroup B vaccine was well tolerated and provided protective immunity in healthy adolescents, according to new findings published in The Lancet.

Miguel L. O’Ryan, MD, of the University of Chile, and colleagues assessed the immunogenicity and tolerability of a four-component vaccine (4CMenB, Novartis) among adolescents aged 11 to 17 years across 12 sites in Santiago and Valparaíso, Chile.

During the observer-blind, placebo-controlled study, 1,631 participants were randomly assigned to one, two or three doses of the candidate vaccine or placebo at 1-, 2- or 6-month intervals.

Serum bactericidal activity (hSBA) was assessed against strains for individual vaccine antigens. Local and systemic reactions were examined 7 days after each vaccination.

Data support the use of the candidate vaccine in a two-dose regimen, according to the results, because 99% to 100% of those who received two or three doses had hSBA titers of at least 4 against test strains, indicating protection vs. 92% to 97% with one dose (P< .0145) and 29% to 50% among those assigned placebo.

Compared with 73% to 76% of those who received one dose of the vaccine that had sustained titers of at least by 6 months, 91% to 100% of those who received two or three doses had sustained titers of at least 4 at 6 months. No serious adverse events were reported.

“The vaccine should be introduced into countries with significant disease impact caused by meningococcus B in the near future,” O’Ryan told Infectious Diseases in Children. “We hope to expect a significant reduction of cases, deaths and sequelae over time in the countries that include the vaccine in their national programs.”

In an accompanying editorial, David S. Stephens, MD, of Emory University School of Medicine in Atlanta, wrote: “The 4CMenB vaccine could be a key to the future prevention of serogroup B meningococcal disease and is the result of over a decade of concentrated effort. The investments in this vaccine have been substantial and might not be repeated, but important questions remain. … The effects of the vaccine on overall meningococcal carriage and on prevention of disease due to other meningococcal serogroups remain important unknown variables. Also, since immunological memory is not a reliable predictor of protection against meningococci, long-term persistence of hSBA concentrations (greater than 6 months) after the two-dose series of 4CMenB vaccines needs to be defined.”

For more information:

• Santolaya ME. Lancet. 2012;doi:10.1016/S0140-6736(11)61713-3.
• Stephens DS. Lancet. 2012;doi:10.1016/S0140-6736(11)61934-X.

Disclosure: This research was funded by Novartis Vaccines and Diagnostics.

Stan L. Block

Almost nothing strikes more fear into the heart of a pediatrician or ED physician than a patient who is strongly suspected of being infected with meningococci. Or even worse sometimes, the child whose diagnosis is missed. I have observed 10 cases of meningococcemia in my general pediatric practice over 30 years. This year, a 4-year-old child presented to me with more than the usual febrile illness. She had moderately severe but nonsurgical abdominal pain, fever (102.5°F), joint aches and was quite cranky. My initial WBC was 14,000/mm³, and her UA and chest radiograph were normal. She improved during the 2 hours I had her in the office, and she was asked to return if any worsening symptoms. She wound up in the ED that night for a recurrence of abdominal pain, and was referred and admitted to tertiary care with evaluations by excellent pediatric surgeons.

With two different consultations, they determined she had a viral gastrointestinal and a non-surgical illness. They were correct. However, during the first 2 days in the hospital with her major abdominal pain, she also had low grade fever and developed some petechial/ecchymotic rash mostly on her legs and lower trunk. Bad abdominal pain, minimal fever plus purpuric lower body rash "equals" Henoch-Schonlein purpura. Wrong. Fortunately she did not deteriorate, as her blood culture from the community ED grew Neisseria meningitidis type B at 72 hours and appropriate antibiotic therapy was then initiated. She developed no sequela, unlike about one-quarter of cases. Lesson: Blood cultures may still be helpful (rarely) in febrile, more ill-appearing children; and meningococcemia may have arthralgias or abdominal pain as major symptoms.

The rate of meningococcal disease in a 4-year-old is about 1 in 100,000. Lucky me. I hate meningococcemia. It can elude even our best physicians. It is a combination of skill, and sometimes luck, that saves our children. See the PBS documentary on meningococcal disease that is part of the Healthy Body Healthy Mind series titled, "Catching a Killer: Preventing Meningococcal Disease."

The sooner we can prevent any significant number of cases of meningococcal disease (now the most common cause of pediatric sepsis and meningitis), the better for patients and doctors. With the routine use of the quadrivalent MCV vaccine (MCV4; serogroups A, C, W-135 and Y) in preteens/teens, serogroup B will soon become the major player, especially since it accounts for up to 60% of all meningococcal cases in those younger than 1 year, who have the highest incidence of disease as well. No vaccine is available for this age.

But meningococcal group B is a crafty, highly complex and elusive pathogen. The scientists at Novartis have manufactured a four-component meningococcal B vaccine (4CMB) to capture some major immunogenic surface components. Investigators like the ones in Chile and in our office have been vigorously testing the new meningococcal B vaccines in preteens, teens and young adults. Two doses of the vaccine looks highly immunogenic and durable (up to 6 months) at this age. However, the following caveats to the current data will need to be addressed or assessed.

Adverse events:

• The very late development of two cases of juvenile rheumatoid arthritis (170 and 198 days); probably serendipitous, as it has not been reported in other recipients.
• 18% rate of severe (but transient) injection site pain cumulatively for all doses; this could possibly hamper acceptability of a second dose in a non-trial setting.

Unknowns/Cautions:

• Wide geographic and variable distribution exists for the two different families of B sub-serotypes; but so far the 4CMB vaccine covers ~87%.
• Most children in this trial already had seropositive titers, thus the vaccine would act more like a booster dose for them. How immunogenic are the two doses in seronegative [US] children?
• Will there be interference with the already routinely recommended vaccines for adolescents (HPV, Tdap)? … And eventually for the infants (the optimal vaccine target) when it arrives for them?
• Problematic acceptability and logistics of an additional two or three shots, and the additional cost of a different meningococcal vaccine for a rare disease? Ideally, the current MCV4 would be combined with any new meningococcal B vaccines to reduce the complexities and costs of two different vaccines.
• Durability; but 6 months post-vaccine titers look outstanding.

One major coup for this novel 4CMB vaccine could be the fact that its surface antigens appear broadly conserved in nearly all the current types, including A,C, Y, W-135 and even X. Could a single vaccine cover nearly all meningococcal serotypes? One could hope. Proving it will be complicated. These scientists are to be congratulated on the first step of their complex journey.

Stan L. Block, MD
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Block reports no relevant financial disclosures.

Philip A. Brunell

The authors make yet another attempt to develop a vaccine against meningococcus group B. This is the major cause of this disease in infants younger than 1 year of age in the United States. It also is an unaddressed cause of disease in all age groups. Previous attempts to produce a group B vaccine have yielded disappointing results. In that, within this group, there are several strains and vaccines that have been successful against some strains (ie, in Cuba and New Zealand), that have not been protective against others. The true test of this vaccine will be its efficacy in clinical trial in areas affected by diverse strains of group B meningococcus.

Philip A. Brunell, MD
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Brunell reports no relevant financial disclosures

Follow the PediatricSuperSite.com on Twitter.