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Published on: January 31, 2018
[From a pathogen's genome to an effective vaccine: the four-component meningococcal serogroup B vaccine]
R Abad1, F Martinón-Torres, M E Santolaya
1Raquel Abad, Laboratorio de Referencia para Meningococos, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo Km. 2,200, 28220 Majadahonda, Madrid, Spain. rabad@isciii.es.
Abstract:
Invasive meningococcal disease (IMD), caused by the bacterium Neisseria meningitidis, entails significant mortality and morbidity. Disease incidence is highest in infants <1 year and young children globally. In Europe, N. meningitidis serogroup B is responsible for over 50% of overall IMD cases, whereas the majority of IMD cases in Latin America is caused either by serogroup B or C. The development of an effective vaccine against serogroup B has challenged the researchers for over half a century. Serogroup B capsular polysaccharide was an inappropriate vaccine antigen, and the success of outer membrane vesicle (OMV) vaccines was restricted to homologous bacterial strains. Reverse vaccinology led to the development of a 4-component meningococcal vaccine including three novel antigens, and OMVs (4CMenB). Each vaccine component has a different target. 4CMenB has been authorised based on its immunogenicity and safety data because the low disease incidence precluded formal clinical efficacy studies. Human serum bactericidal antibody (hSBA) assay tests functional antibodies in the serum of vaccinated individuals (i.e. the vaccine immunogenicity), and is the accepted correlate of protection. Vaccine strain coverage has been assessed both through hSBA assays and a more conservative method named Meningococcal Antigen Typing System (MATS). Effectiveness data of 4CMenB have been collected in the field since 2013. The vaccine proved effective in outbreak control in North America, and recent data from the introduction of the vaccine in the United Kingdom infant national immunisation programme reveal a vaccine effectiveness of 82.9% for the first two doses, with an acceptable safety profile.
Insights
A new 4-component meningococcal vaccine (4CMenB) shows high effectiveness (82.9%) in infants against serogroup B invasive meningococcal disease (IMD). This vaccine, developed using reverse vaccinology, offers protection against a leading cause of infant mortality and morbidity.
Area of Science:
- * Vaccinology and immunology
- * Bacterial pathogenesis and disease prevention
- * Public health and epidemiology
Background:
- * Invasive meningococcal disease (IMD), caused by *Neisseria meningitidis*, presents significant global mortality and morbidity, particularly in infants.
- * *Neisseria meningitidis* serogroup B is a primary cause of IMD in Europe and Latin America, posing a long-standing vaccine development challenge.
- * Previous vaccine approaches, including capsular polysaccharide and strain-specific outer membrane vesicle (OMV) vaccines, had limitations.
Purpose of the Study:
- * To evaluate the effectiveness and safety of the 4-component meningococcal vaccine (4CMenB) against serogroup B IMD.
- * To assess the immunogenicity of 4CMenB using human serum bactericidal antibody (hSBA) assays and Meningococcal Antigen Typing System (MATS).
Main Methods:
- * The 4CMenB vaccine was developed using reverse vaccinology, incorporating novel antigens and OMVs.
- * Vaccine immunogenicity was assessed via hSBA assays, a correlate of protection.
- * Vaccine effectiveness was evaluated through field data collection since 2013, including analysis of outbreak control and national immunisation programme data.
Main Results:
- * The 4CMenB vaccine demonstrated significant effectiveness, reaching 82.9% for the first two doses in a UK infant national immunisation programme.
- * The vaccine has shown efficacy in controlling outbreaks in North America.
- * 4CMenB exhibits an acceptable safety profile.
Conclusions:
- * The 4CMenB vaccine is an effective tool for controlling serogroup B invasive meningococcal disease, especially in vulnerable infant populations.
- * Reverse vaccinology has successfully yielded a broad-coverage vaccine against a challenging pathogen.
- * Real-world data confirm the vaccine's effectiveness and acceptable safety, supporting its role in public health immunization strategies.
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