Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 14th International Congress on Infectious Diseases (ICID)

Miami, Florida / March 9-12, 2010

The epidemiology of invasive meningococcal disease changes over time and varies depending on geographic location and season. The incidence also affects various age groups differently as does their susceptibility to circulating serogroups that cause the disease. Nationally, the incidence of invasive meningococcal disease per 100,000 population in 2006—the last year for which complete data are available—was 0.66, with 210 cases reported during that year overall. Slightly over half of them were attributable to serogroup B, 20% to serogroup C, 13% to serogroup Y, 3% to serogroup W-135, 1% to serogroup A and 9% to other serogroups.

Importantly, however, the proportion of disease caused by the five main serogroups varies quite considerably from province to province, and individual serogroups may cause anywhere from none to extremely little disease to relatively substantial proportions of it. Decisions as to which vaccine should be offered to respective age groups thus must take into consideration the local epidemiology of the disease.

Since 2001, the National Advisory Committee on Immunization (NACI) has recommended the use of the meningococcal C conjugate vaccine for specific age groups. Recently, they also recommended the use of the quadrivalent vaccine in adolescents. The adolescent dose of a conjugated meningococcal vaccine should be included in the routine vaccination schedule, even if the recipient was previously vaccinated as part of a routine infant or 1-year-old meningococcal C vaccination program. The adolescent dose will help to ensure circulating antibody titres against serogroup C which appear to be important for ongoing protection against invasive meningococcal disease. The optimal age for the adolescent dose is about 12 years.

Either the monovalent meningococcal C conjugate vaccine or the quadrivalent conjugate vaccine against ACW-135 and Y may be used in adolescence, the choice being influenced by considerations of local epidemiology.

Towards a Broadly Immunogenic Vaccine

The variability and unpredictability of serogroup distribution nationally and globally suggest that effective control of meningococcal disease requires the use of a vaccine that is broadly immunogenic against multiple serogroups. In this regard, the polysaccharide meningococcal vaccine may not be ideal.

As discussed by Dr. Jamie Findlow, Health Protection Agency, Manchester, UK, polysaccharide vaccines against serogroups A and C are effective in older children and adults and can be useful in helping control outbreaks and epidemics. Conversely, polysaccharide vaccines are poorly immunogenic in children under the age of 2 years and responses to these vaccines cannot be boosted. Moreover, “You need high levels of circulating antibodies to provide protection,” Dr. Findlow added. Polysaccharide vaccines also do not induce immunologic memory, which limits duration of protection to three to five years and they have limited or no impact on nasopharyngeal carriage and therefore do not contribute to herd immunity. Upon re-exposure to the polysaccharide vaccine, some recipients mount a blunted antibody response which may not protect them against disease.

In contrast, the conjugate vaccines induce immune memory and are immunogenic in infants, where the burden of meningococcal disease is highest. Experience with the meningococcal C conjugate vaccine in the UK has shown it reduced nasopharyngeal carriage of serogroup C by 71% to 81%—“Evidence that not only is the vaccine protecting against invasive disease, it provides protection in the nasopharynx and prevents or eradicates carriage,” Dr. Findlow observed. There is also no risk of inducing hyporesponsiveness with repeated exposure to the conjugate vaccine and conjugate vaccines lead to high levels of antibody persistence. Because of these benefits, public health officials in the UK recommend the use of the conjugate meningococcal vaccine in both infants and adolescents as well as at-risk populations and for those who are immunocompromised. Conjugate vaccination may also be the optimal policy for frequent travellers, Dr. Findlow noted, as the use of a conjugate vaccine limits the need for repeated doses.

New Quadrivalent Vaccine

A comparison of a new quadrivalent meningococcal vaccine that includes cross-reacting material (CRM) of a naturally-occurring non-toxic mutant of diphtheria toxin found that the MenACWY-CRM vaccine was non-inferior to the currently available MenACWY-D vaccine (Menactra) in a phase III clinical trials program. In general, more adolescents vaccinated with the new MenACWY-CRM vaccine responded to all four serotypes than those who received the MenACWY-D vaccine: 75% vs. 66% to serogroup A, 75% vs. 71% to serogroup C, 75% vs. 63% to W-135 and 68% vs. 41% to serogroup Y.

Geometric mean titres (GMTs) one month post-vaccination were also consistently higher among adolescents who received the MenACWY-CRM vaccine than those who received the MenACWY-D vaccine. The percentage of adolescents with human complement (hSBA) titres =1:8 was also significantly higher for serogroups A, W-135 and Y, while rates of systemic reactions were similar in both vaccine groups. Concomitant administration of the MenACWY-CRM vaccine with several other routine vaccinations in adolescence did not affect immune response of either vaccine.

Among adults between 19 and 55 years of age, seroresponses were also significantly higher against serogroups C and Y in MenACWY-CRM recipients than MenACWY-D recipients. The percentage of adults who achieved hSBA titres =1:8 was also significantly higher for serogroups C and Y with the new vaccine, while GMTs were significantly higher as well against C, W-135 and Y in MenACWY-CRM recipients than in MenACWY-D recipients.

Persistent Antibody Titres

Not only is it imperative that vaccinees mount a high enough antibody response to vaccine serotypes to protect them against invasive disease, antibody titres must remain high over time in order to ensure that protection against invasive disease is durable. As discussed here during the scientific sessions, the new MenACWY-CRM vaccine has robust evidence supporting persistent antibody responses out to 22 months post-vaccination.

At a mean follow-up of 22 months in the phase III trial in adolescents, the proportion of patients with hSBA =1:8 against serogroups A, C, W-135 and Y were 36%, 62%, 84% and 67%, respectively, compared with 25%, 58%, 74% and 54% against the same four serogroups for MenACWY-D recipients, respectively, reported Dr. Christopher Gill, Cambridge, Massachusetts (Figure 1). GMTs at 22 months were also consistently higher for all four serogroups among MenACWY-CRM recipients as were the proportions of MenACWY-CRM vaccinees with hSBA =1:8 for serogroups A, W and Y; GMTs were also significantly higher for serogroups A and Y in the same recipients.

Thus, investigators concluded, the majority of adolescents maintain bactericidal antibody titres of about 1:8 against serogroups C, W-135 and Y two years after receiving either conjugate vaccine although more MenACWY-CRM vaccinees still had protective antibody titres against serogroups A, W-135 and Y than those who received the MenACWY-D vaccine.

Figure 1.

Recommendations for Travellers

Canadian experts now recommend travellers receive a meningococcal vaccine under specific circumstances, preferentially a conjugate vaccine. “W-135 and Y make up a significant proportion of meningococcal disease now in Canada so why would you not give a conjugate quadrivalent vaccine,” commented Dr. Jay Keystone, Director, Toronto Medisys Travel Clinic, Ontario, in an interview. For travellers, “I would say, absolutely immunize with the conjugate vaccine,” he added, as experience with the polysaccharide vaccine showed that pilgrims travelling to high-risk areas may not become symptomatic themselves but that they bring the disease back to their homeland where they infect others. The new MenACWY-CRM quadrivalent vaccine does provide higher seroprotective rates and higher antibody levels than the currently available quadrivalent vaccine, “so it may turn out to be a better vaccine,” Dr. Keystone suggested. Notably, however, efficacy trials cannot be carried out comparing the two vaccines as there are too few cases of meningococcal disease to make this feasible. “In theory, there may be an advantage for the MenACWY-CRM vaccine, but in practice I believe they will prove to be equally excellent vaccines,” Dr. Keystone stated.