Review article
The long and winding road towards a MenB vaccine with broad strain coverage
Johan Holst
; Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
Abstract
The Minister of Health for the UK was advised by an expert committee meeting in February 2014 to include a new, broad-spectrum meningococcal serogroup B (MenB) vaccine, 4CMenB (Bexsero®) into the childhood immunization program. This new vaccine which recently received regulatory approval in Europe, Canada and Australia combines a conventional wild-type outer membrane vesicle (wtOMV) vaccine and antigens identified through reverse vaccinology. Strain coverage estimates from different parts of the world are in the range of 70% to 90%, depending on the local epidemiological situation. Following implementation of this vaccine, monitoring should focus on effectiveness data for various circulating strains and potential vaccine effects on carriage and herd immunity. From use of this new MenB vaccine on a larger scale and good monitoring in UK and other countries that are likely to follow shortly, the international vaccine community will learn a number of lessons. Such insights will be important for further improvement towards later generations of MenB vaccines and other protein-based vaccines against various diseases. Herein sights gained from more than 35 years of development and use of MenB vaccines are presented. The novel vaccine, 4CMenB represents a new time horizon in protein-based vaccine formulation, evaluation and value. Importantly, 4CMenB was developed with "cutting edge" joined with conventional vaccine technology, including experience from previous wtOMV vaccines, which have been successfully used since the late 1980s to prevent clonal outbreaks. Data from large clinical studies and retrospective statistical analyses give effectiveness estimates of at least 70% and a consistent pattern of moderate reactogenicity during the use of >80 million doses of three different wtOMV vaccine formulations. The key limitation of these wtOMV vaccines is the immunodominant response against the hypervariable PorA protein (especially in infants) and their likely inability to control disease in a population where the circulating strains are highly diverse. In New Zealand from 2004 to 2008, the wtOMV vaccine MeNZB® was used to control a clonal MenB epidemic. This public health intervention provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness-estimation and communication to the public. Thus, 4CMenB marks a new paradigm and represents the use of historical knowledge at the same time. Finally, the world now has the possibility to use a vaccine which is designed to give more comprehensive protection in epidemiological situations where circulating strains are very heterologous with respect to the genetic and antigenic properties. The historical integration of knowledge represented by 4CMenB will also prove important for other vaccine development in the time to come.
Keywords
Neisseria meningitidis; meningococcal disease; wtOMV vaccines; universal multicomponent MenB vaccine
Hrčak ID:
133458
URI
Publication date:
30.6.2014.
Visits: 3.130 *