Meningococcal vaccine appears safe when administered with other vaccines

Stan L. Block, MD

Few people in general pediatric practice dread or fear meningococcemia as much as I do (I think). In my 30-year career in rural Kentucky, I provided emergency care for 10 patients with this highly lethal disease that makes my won pulse pound. Unlucky me, I guess, but luckily/happily they all survived. (See www.HealthyBodiesHealthyMinds.org, “Catching a killer,” produced by PBS television.)

Our office and others have been involved in many research trials evaluating the three new meningococcal vaccines for infants and toddlers. Subsequently, infants in the US now have two FDA-approved options for meningococcal vaccination: 1) four doses of a combination HiB Mening-CY (bivalent) (MenHibrix, GlaxoSmithKline) at ages 2, 4, 6 and 12 months; and 2) two doses of the diphtheria conjugate quadrivalent Men ACWY-D (Menactra, Sanofi) at ages 9 and 12 months. The third option, Men ACWY-CRM (four doses) MenACWY-CRM (Menveo, Novartis Vaccines and Diagnostics), for infants is still being reviewed by the FDA.

The recent article in the August issue of the Pediatric Infectious Disease Journal provides further evidence regarding the good meningococcal serotype immunogenicity and minimal reactogenicity of the MenACWY-D vaccine evaluated in 3,000 patients of the toddler age group (doses at 9 and 12 months). It also showed some low-level interference with the antibody concentrations produced by 7-valent pneumococcal conjugate vaccine (Prevnar, Pfizer) vaccine the two were administered concomitantly at age 12 months. However, it did not significantly reduce the geometric mean titers (GMTs) to ineffective concentrations or, more importantly, did not reduce the rate of children who seroconverted with the seven pneumococcal strains in PCV7. 

Two caveats regarding possible interference: We still have no data on concomitant administration at aged 12 months of MenACWY-D with the six other serotypes in the 13-valent pneumococcal conjugate vaccine (Prevnar13, Pfizer), which is now the standard; or concomitant with combined diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus and Haemophilus influenzae b conjugate vaccine (Pentacel, Sanofi) vaccine at ages 15 to 18 months.

Unlike this study, an earlier trial showed some statistical reduction of GMTs in a few PCV7 serotypes (4, 6B and 18C) with concomitant MenACWY-D. But all PCV7 titers were still “robust,” per the CDC Advisory Committee on Immunization Practices’ (ACIP) evaluation (MMWR. 2011; 60(40);1391-1392).

ACIP has given a “permissive recommendation” for routine two-dose administration of MenACWY at ages approximately 9 and approximately 12 months. We are still waiting for their assessment of the HiB MenCY at 2, 4, 6 and 12 months, which also produces excellent Hib antibody titers. Until the meningococcal vaccines are formally “recommended,” this translates both to minimal routine office use — and also minimal to moderate commercial insurance coverage of the vaccines. The latter can be a real economic gamble for all private pediatric office practices.

Nonetheless, MenACWY-D was still recommended for those uncommon children aged 9 to 24 months who are at “high risk” for meningococcal disease.

Finally, about 150 (16%) of approximately 1,000 invasive meningococcal disease cases annually occur in infants younger than 1 year of age — the largest age burden in any age group. But remember that meningococcal serotypes C, Y and B predominate in infancy, with serotype B accounting for more than half of isolates. We have no meningococcal B vaccine yet (we are working on that vaccine now).

Thus, an infant vaccine containing C and Y administered at ages 2, 4, 6 and 12 months could protect about 50% of known invasive cases each year in children younger than 2 years. In order for a 9- and 12-month dose of C and Y vaccine (MenACWY-D) to protect almost as many of these younger children, it would likely need to rely more upon the herd protection phenomenon, as some authors have predicted (Ortega-Sanchez I; Slides from October 2011 ACIP Meeting, www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-oct11/03-MCV-Ortega-Sanchez.pdf; accessed Aug. 3, 2012).

The real missing data link is the unknown number of cases of meningococcal invasive disease that physicians inadvertently missed with our outpatient sick child policy of: 1) high fever; 2) high blood WBC; and 3) no blood culture – which are then empirically treated with parenteral ceftriaxone.

Thus, the cost-to-benefit ratio and routine recommendations for these three new meningococcal vaccines with serotypes C and Y for infants is under major debate.