The price of prevention: what now for immunisation against meningococcus B?

Abstract

www.thelancet.com Vol 382 August 3, 2013 369 Meningococcal sepsis is one of the most dreaded bacterial infections: the death rate remains at about 5% and the eff ects for survivors include neurological damage, limb amputation, and widespread skin necrosis. There is a compelling case for prevention of meningococcal disease by immunisation. On July 24, 2013, in an interim position statement, the UK Joint Committee on Vaccination and Immunisation (JCVI) concluded that it cannot currently recommend a vaccine (4CMenB, licensed as Bexsero, Novartis Vaccines and Diagnostics, Siena, Italy) for use in the UK routine immunisation programme. Many will be disappointed that for the time being meningococcus B will continue to exact its toll of deaths and dis abilities. There have been more than 10 000 cases of meningococcal B disease in England and Wales during the past 10 years. In the past two decades, vaccines against strains of meningococcal sepsis other than meningococcus B have been developed and included in routine or selective immunisation programmes. However, it had not been possible to develop a vaccine suitable for routine use to prevent disease caused by meningococcus B, the most common cause of sepsis and meningitis in the UK and in many other countries. Currently used meningococcal vaccines are based on inducing antibodies to the major virulence factor of the meningococcus, its capsular polysaccharide. This approach was not feasible in the case of strains of meningococcus B because its capsule, a homopolymer of sialic acid, is a poor immunogen. In 1997, a vaccine research and development project began that used the complete genome sequences of a meningococcus B strain to provide an inventory of every potential vaccine antigen, an innovation now widely known as reverse vaccinology. From the many hundreds of possible candidate antigens, a multicomponent vaccine was formulated. The safety and immunogenicity of 4CMenB has been evaluated in clinical trials in which more than 7500 participants have received the vaccine. In November, 2012, the European Medicines Agency approved the vaccine and European Commission licensure followed in January, 2013. The stage was set for immunisation programmes to include vaccines against all the major causes of non-neonatal acute bacterial meningitis. A major responsibility of the JCVI, the advisory body to UK health departments on immunisation, is to assess the cost-eff ectiveness of vaccines. The JCVI concluded that routine immunisation using 4CMenB is highly unlikely to represent value for money at any vaccine price—ie, the costs of implementing the vaccine would be greater than those resulting from the impact of meningococcus B. Their conclusion was based in large part on an unpublished report “developed to take into account advice from the JCVI sub-committee” and conducted by the same academic institutions that recently concluded that the vaccine would be cost eff ective if competitively priced. An independently conducted Dutch study emphasises how sensitive costeff ectiveness analyses are to both disease incidence and vaccine price. Importantly, the manufacturer of 4CMenB has not made any announcement on the price of the vaccine and strongly contests the JCVI’s conclusions. In assessing cost-eff ectiveness, a major factor is whether 4CMenB can prevent person-to-person spread of meningococci through a reduction in upper-respiratory tract carriage, thus potentially providing protection to those people who have not been immunised. The JCVI notes that the licensure of 4CMenB was based on clinical trials that did not include a direct demonstration of vaccine effi cacy—ie, prevention of disease. But the JCVI acknowledges that the relative rarity of meningococcal disease had precluded any realistic possibility of a classic effi cacy trial. This is why it has been agreed for licensing purposes that the only practical solution is to use a surrogate of protection: the capacity of the sera of immunised individuals to kill the relevant strains of meningococcus B in a laboratory assay. To obtain data on effi cacy, duration of protection, and reduction in carriage, the vaccine would need population-based evaluation, most effi ciently through post-implementation surveillance following introduction into the routine immunisation programme. However, this was the situation in November, 1999, when the decision about the introduction of the meningococcal C vaccine into the The price of prevention: what now for immunisation against meningococcus B?

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