In a study published Online First in The Lancet, researchers have examined the efficacy of a new vaccine against serogroups of Neisseria meningitides, which unlike the four out of six existing safe and efficacious vaccines, also includes protection against serotype B. Serogroups of Neisseria meningitides cause meningococcal diseases, including meningitis. Even though serotype B is the most prevalent strain across South America, it is also common in high-income countries causing much of the remaining meningococcal disease burden.

The latest licensed vaccines against serotype B, or those in the final stages of development, only protect against the other four major strains, such as serogroup A, C, W135, and Y because of serotype B’s challenging immunogenic properties. Recently, a sixth serogroup X has emerged in outbreaks in Africa and is being closely monitored.

At present, the ACWY vaccine is used to protect people against four of the serotypes in the United States, whilst in Europe routine childhood vaccination with serogroup C meningococcal conjugate vaccines, which only protect against this particular serotype, have been successfully implemented. This has resulted in serogroup B becoming a major cause of meningococcal disease in Europe and other continents, presenting a significant medical and societal burden. For example, in the UK, almost 19% of incidents of invasive serogroup B disease that has been confirmed by a laboratory proved fatal between 1999 and 2006. The prevalence of serogroups B, C and Y is nearly the same in North America, yet the population remains unprotected against serogroup B. In the southern parts of Latin America, where serotype B is most prevalent, more than 60% of Chileneans are infected with this serogroup.

The researchers used whole genome sequencing to identify proteins on the surface of many meningococcal strains in their quest to develop a broad-spectrum vaccine against serogroup B. This method can potentially be applied to target all other serogroups. The vaccine that has been developed to target strain B, called 4CMenB, includes four components that target various parts of the bacterium.

The researchers conducted a randomized, placebo-controlled trial of 4CMenB, at 12 sites in Santiago and Valparaíso in Chile. Children and teenagers between the ages of 11 and 17 years received one, two, or three doses of 4CMenB 1 month, 2 month or 6 month intervals.

During the primary phase, the researchers first randomized the participants into five groups (3:3:3:3:1) to receive either one or two doses in monthly or 2-monthly intervals, three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All participants were administered with at least one dose of 4CMenB.

In total, 1,631 adolescents aged on average 14 years, received at least one dose of 4CMenB. They discovered that after two or three doses, almost all, i.e. 99 to 100% of participants showed hSBA titers of 4 or more against test strains, indicating protection, compared with 92 to 97% after one dose, and 29 to 50% after placebo. At 6 months, 91 to 100% of participants still showed titers of 4 or more for each strain after two or three doses, yet only 73 to 76% showed titers of 4 or more after one dose.

At 6 months, seroresponse rates achieved 99 to 100% for each strain after the second or third doses. The researchers observed that local and systemic reaction rates were comparable, following each 4CMenB injection, and did not increase with later doses, yet remained higher compared with placebo. The researchers observed no vaccine-related serious adverse events and detected no important safety signals.

The study has now been completed with regard to the vaccine’s efficacy for children, adolescents and adults, with all findings displaying similar, positive results. The researchers comment:

“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 conclude: “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.”

Dr David S Stephens at the Emory University School of Medicine in Atlanta, GA, USA, and the VA Medical Center in Atlanta, GA, USA, states in an associated comment:

“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 questions the need for additional booster doses to maintain protective efficacy. This is particularly significant if the vaccine is targeted at infants and young children, who represent a major risk group for serogroup B disease.

He concludes saying: “Data are also needed for concurrent administration of 4CMenB with other vaccines, which are components of routine immunization. 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.”

Written by: Petra Rattue