New Vaccine Against Group B Meningococcal Disease to Target This Largest Remaining Source of Such Disease in Europe, North America, and Some Developing Regions

Safe and efficacious vaccines exist for protection against four out of the six major serogroups of Neisseria meningitidis, which cause meningococcal diseases, including meningitis. A study published Online First by The Lancet analyses the efficacy of a new vaccine that includes protection against serotype B, which causes much of the remaining meningococcal disease burden across high-income countries (where it is common) and also regions such as South America (where it is the most prevalent strain). The Article is by Professors María Elena Santolaya and Miguel L O'Ryan, University of Chile, Chile, and colleagues.

Due to the challenging immunogenic properties of serotype B, the latest vaccines that are either licensed or in final stages of development only protect against the other four major strains: serogroup A, C, W135, and Y. A sixth serogroup, X, has only recently emerged in outbreaks in Africa, and is being closely monitored.

In the USA, the ACWY vaccine is currently being used to protect people against four of the serotypes. In Europe, there has been successful implementation of routine childhood vaccination with serogroup C meningococcal conjugate vaccines (these only protect against serotype C). As a result serogroup B is now the major cause of meningococcal disease in Europe and elsewhere, with a substantial medical and societal burden. In the UK, for example, up to 19% of laboratory-confirmed cases of invasive serogroup B disease between 1999 and 2006 were fatal. In North America, prevalence of serogroups B, C, and Y is almost equal, but the population remains unprotected against serogroup B. In the southern cone of Latin America, serotype B is the most common, with over 60% of meningococcal disease cases in Chile caused by this serogroup.

To develop broadly protective vaccines against serogroup B, whole genome sequencing was used to identify proteins on the surface of many meningococcal strains (a method that could potentially be used to target all the other serotypes). The vaccine developed to target strain B (4CMenB) includes four components targeting various parts of the bacterium. The randomised, placebo-controlled, trial of this vaccine took place at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB.

Overall, 1631 adolescents (mean age 14 years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains (indicating protection), compared with 92-97% after one dose and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose;seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified.

This research team and others have now completed studies into efficacy of this vaccine for adults, children, and adolescents, all yielding similar, positive results. The authors say: "This pivotal study shows that two doses of the novel 4MenCB vaccine separated by 1, 2, or 6 months provide a potentially protective immune response in almost 100% of adolescents irrespective of previous antibody status. Actual levels of protection will depend on geographical variation of strains...Further study is needed to provide information about the immunogenicity and tolerability of 4CMenB in various age groups, including infants, who bear the largest disease burden worldwide."

They add*: "Development of a broadly protective vaccine against meningococcus B has been a longstanding challenge in order to provide more comprehensive protection against the most common pathogenic meningococcus. Currently this is the predominant strain in Europe and is a substantial contributor to the disease burden in the United States, in large part due to the control of the other strains with effective MenC or MenACWY vaccine strategies. In this context, adding a meningococcal B vaccine as a standalone or eventually combined vaccine can be foreseen for both regions in the near future. The urgency will depend on the incidence of meningococcal B disease, currently higher in some European countries than in the United States."

In a linked Comment, Dr David S Stephens, Emory University School of Medicine, Atlanta, GA, USA, and VA Medical Center, Atlanta, GA, USA, says: "A preliminary study suggests that 73-87% of circulating serogroup B strains in five European countries would be covered by the vaccine, but more data are needed. Implementation recommendations will depend on country-specific incidence of serogroup B and vaccine coverage."

Dr Stephens also asks whether additional booster doses would be needed to maintain protective efficacy, especially important if the vaccine is targeted to infants and young children, a major group at risk for serogroup B disease. He concludes: "Data are also needed for concurrent administration of 4CMenB with other vaccines, which are components of routine immunisation. These questions might not be fully answered before licensure and implementation of the 4CMenB vaccine, but are crucial to widespread use and population-specific recommendations. Serogroup B meningococcal disease remains a serious global health problem and prevention of serogroup B disease could be a step closer with new serogroup B vaccines."

Taken from www.thelancet.com/journals/lancet/.