ACIP recommends off-label MCV4 use for certain high-risk individuals

Health care providers may soon be able to administer a second dose of meningococcal polysaccharide diphtheria toxoid conjugate vaccine to individuals at increased risk for meningococcal disease several years following their first vaccination.

Amanda Cohn, MD, of the Division of Bacterial Diseases at the National Center for Immunization and Respiratory Diseases presented the rationale for her working group’s recommendation to the CDC’s Advisory Committee on Immunization Practices meeting, held in Atlanta this week.

Although the MCV4 package insert currently only supports a one-dose indication, Cohn explained the working group’s proposals were based “out of an abundance of caution,” stating that “limited off-label use in a small targeted group may be useful.”

The recommendation states that children aged 2 to 6 years who remain at increased risk for meningococcal disease following administration of the first dose of meningococcal polysaccharide diphtheria toxoids conjugate vaccine (MCV4, Menactra, Sanofi Pasteur) may be revaccinated with MCV4 three years following initial vaccination and that individuals aged 7 to 55 years should receive a second dose five years after first vaccination. This applies to the following populations:

Individuals with persistent inherited or chronic complement component deficiencies, such as C3, properdin, factor D or late complement components.
Those with functional or anatomical asplenia.
Microbiologists who are routinely exposed to high bacterial loads of Neisseria meningitidis.
People who frequently travel to or who live in areas with high rates of meningitis.

These provisions were recommended following concerns about waning functional antibody response and demonstrated disease risk in this small population, coupled with low risk for adverse events.

Cohn explained the elevated risk for mortality among laboratory workers, citing a small survey (n=16) by Sevjar et al published in a 2005 edition of the Journal of Clinical Microbiology. Using this data she projected the mortality rate for this population was 13 per 100,000 vs. 0.3 per 100,000 amongst the general population.

“High levels of antibody are important for those working in high risk environments, and persons with complement deficiency and asplenia who are not protected by herd immunity in the population,” Cohn said. “Evidence supports a boost response to revaccination.”

MCV4 was initially licensed in 2005 and indicated only for single-dose administration based on the assumption that the conjugate vaccine would likely provide a longer duration of protection than the polysaccharide meningococcal vaccine (MPSV4, Menomune, Sanofi Pasteur).

Although limited available data suggest substantially more patients aged 11 to 18 years had higher antibody titers three years following receipt of the initial MCV4 dose (74.6% had serogroup C SBA-BR titers of 1:128, n=71) compared with patients who received one MPSV4 dose (59.7% had serogroup C SBA-BR titers of 1:128, n=72), the geometric mean titers to serogroup C decreased dramatically among another cohort three years post vaccination.

This data was not enough to convince working group members that a single dose of MCV4 provides better protection to recipients than those who are unvaccinated or who have received MPSV4, according to Cohn.

The revaccination recommendations would not apply to college freshman or military recruits, as vaccination coverage rates among these groups are high, increasing the likelihood of herd immunity. – by Nicole Blazek

For more information:

Cohn A. Rationale and proposed recommendations for revaccination of persons at increased risk for meningococcal disease. Presented at: the Advisory Committee on Immunization Practices Meeting; June 24-26, 2009; Atlanta.

It is now realized that boosters with polysaccharide vaccines do not actually boost, but in fact may cause a reduction in antibody protection. In contrast all conjugate vaccines, including MCV4, will boost immune responses. For diseases like meningococcal meningitis and septicemia the time from nasopharyngeal colonization to bloodstream invasion can be a matter of hours, so having a circulating level of protective bactericidal antibody may prove critical to protection. Simply stated, immune memory responses that take three to seven days to produce protective antibody serum may not be fast enough. This recommendation is well founded.

– Michael Pichichero, MD

Infectious Diseases in Children Editorial Board