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 - 28th Annual Meeting of the European Society of Pediatric Infectious Diseases (ESPID)

Nice, France / May 4-8, 2010

Meningococcal disease continues to cause significant morbidity and mortality in developed countries and pandemics in sub-Saharan Africa. The predominance of the different serogroups responsible for meningococcal disease is also shifting and the group C serotype targeted by earlier vaccines is becoming less dominant in certain populations. This may well reflect the overriding trend towards global travel, which is contributing to the changing meningococcal disease profile.

“Meningococcal invasive disease remains a serious public health concern worldwide,” Dr. Muhamed-Kheir Taha, Institut Pasteur, Paris, France, cautioned. “The number of countries reporting epidemics is increasing and the incidence is varying with age, with a second peak occurring in young adults.”

Protective Effects of Mass Immunization

The changing epidemiological profile of meningococcal disease has been especially well-documented in the UK, where a mass immunization campaign followed outbreaks of serogroup C disease in 1999 to 2001. During the campaign, the monovalent meningococcal conjugate vaccine was used in children aged 5 months to 18 years. Routine three-dose vaccinations followed for infants 2, 3 and 4 months. Although disease levels have remained low since, Dr. Jamie Findlow, deputy director, Health Protection Agency Vaccination Evaluation Unit (VEU), Manchester Royal Infirmary, UK, emphasized that protection levels against endemic MenC appear to be waning significantly, as has also been observed in Greece, The Netherlands and Spain. “We have seen excellent efficacy with infant-targeted vaccination campaigns persisting for up to one year, but afterwards the efficacy rates dramatically declined,” Dr. Findlow stated, “and we have seen vaccine failures related to declining antibody levels and immunological memory.” Children vaccinated with the polysaccharide conjugate during infancy show steep drops in antibody titres in the second through fifth years of life (to only 10% having preventive titre levels by age 3 to 4).

In contrast, vaccine effectiveness has persisted more strongly in children receiving vaccinations from 5 months to 18 years as was done during the initial UK catch-up campaign. In adolescents, sustained levels of protective antibodies have only been observed following booster administration at =10 years of age. In 2006, public health policy in the UK switched to a 2- and 4-month infant vaccination program followed by a booster at 12 months.

“Booster vaccination at 12 months adequately renews antibody titres to over 90% of children, but even 24 months later they generally drop again to pre-vaccine levels,” Dr. Findlow continued. Since maintenance of protective antibody levels against disease are crucial, they have now reduced the number of priming doses in infants and introduced a boosting dose after 12 months of age in order to achieve more persistent antibodies over a longer period of time.

“We may also be looking at introducing a later vaccine booster dose,” Dr. Findlow added, “and if we use a quadrivalent agent in those who have already been primed for the MenC it acts as a booster for MenC, but also as a renewed priming dose for the A, Y, and W components. A quadrivalent conjugate vaccine offers wider protection than just using a monovalent agent.”

Canadian Perspective

The issue of heightened vulnerability to meningococcal disease in adolescents and young adults was further corroborated by Dr. Philippe De Wals, Université Laval, Quebec. He observed that the problem of waning immunity is compounded in adolescents between the ages of 15 and 22 years when young adults congregate in places such as dormitories that facilitate disease transmission. Since 2001, there have been 17 vaccine failures and meningococcal disease can still be fatal in previously vaccinated recipients.

There has also been a sharp drop in lasting protection following the initial infancy-concentrated vaccination regimen and spikes in disease incidence in the age group of 17 to 21 years. “Adolescents and young adults have particularly high carriage rates for Neisseria meningitides,” Dr. De Wals told delegates, “and our analysis indicates that the most effective program could consist of three doses given at 12 months, 12 years and 18 years.”

Dr. De Wals also reported that their economic analysis indicated that adding an adolescent dose would reduce the burden of disease at no cost. “If you are using a quadrivalent product, the initial cost may be slightly higher but the ultimate result appears to be neutral. Our findings have led us to recommend a booster dose in adolescents through school programs to prolong the immunological memory and also, importantly, to provide herd protection.”

Quadrivalent Vaccine

The efficacy and safety of a new quadrivalent meningococcal vaccine, MenACWY-CRM (Menveo), has been investigated in more than 18,500 infants, children, adolescents and adults. Dr. Roger Baxter, Co-director, Kaiser Permanente Vaccine Study Center, Oakland, California, reported that compared to the currently available quadrivalent vaccine, the new vaccine achieved statistically higher immunogenicity levels for serogroups A, W-135 and Y in adolescents as well as for serogroups C, W-135 and Y in adults. In adolescents, the optimum immune response (the proportion of patients with hSBA titres =1:8) to serogroup A was >80% following vaccination with MenACWY-CRM vs. 40% with the polysaccharide vaccine and for serogroup C, the differential was =85% vs. 60%.

There was also an improved, although less significant, efficacy for serogroups W-135 and Y. MenACWY-CRM, when compared to the MenACWY-D vaccine (Menactra), also showed consistently higher seroresponses to vaccine serotypes. As Dr. Baxter noted, five serogroups cause almost all meningococcal disease in the world, incidence rates being highest in infants with another incidence peak in adolescents. “Protecting children and [other] high-risk groups against as many of these serogroups as possible is the optimal long-term solution,” he concluded.

MenACWY-CRM Findings

During another presentation here during the scientific sessions, Dr. C.J. Gill, Cambridge, Massachusetts, reported that two randomized trials with MenACWY-CRM support the persistence of bactericidal activity in adolescents against serogroups A, C, W-135 and Y. Results from rabbit complement serum bactericidal assays (rSBA) demonstrated that MenACWY-CRM recipients had higher percentages of antibody titres =1:8 for all major serogroups at both 12 and 21 months’ post-vaccination than did those given the comparator vaccines of both MenACWY-D or the polysaccharide vaccine.

In the second 200-patient trial, the rSBA geometric mean titres were higher for MenACWY-CRM recipients at 21 months vs. MenACWY-D, respectively, at 1075 vs. 739 (P=0.2) for serogroup A, 91 vs. 44 (P=0.05) for group C, 792 vs. 280 (P=0.002) for group W-135 and 564 vs. 115 (P=0.001) for group Y, Dr. Gill reported. MenACWT-CRM has also demonstrated an equivalent immune response to the polysaccharide vaccine in adult populations aged 56 to 65 years.

Recommendations

The American Academy of Pediatrics now recommends routine vaccination for all persons 11 to 18 years of age and vaccinations for everybody 2 to 55 years old who is in a high-risk group, including college freshman, international travellers and the immune-suppressed. In Canada, since 2009, the National Advisory Committee on Immunization (NACI) recommends that a dose of meningococcal conjugate vaccine be offered in early adolescence, ideally at around 12 years of age, even if the adolescent was previously vaccinated as part of a routine infant or toddler vaccination program.

This adolescent dose is to ensure that circulating antibodies are present as adolescents enter the peak years for invasive meningococcal disease beyond infancy, which are between 15 and 24 years of age. It is now widely accepted that the anamnestic response cannot be depended on to prevent disease and that circulating antibodies are needed for protection due to the disease’s short incubation period.