Abstract
ObjectiveAlthough the incidence of meningococcal disease has been declining over the past decade in Portugal MenB meningococci is still an important cause of meningitis and sepsis. The aim of this study was to estimate the strain coverage of the 4CMenB vaccine in Portugal in order to support health policies for prevention and control of meningococcal disease.MethodsSince 2002 the clinical and laboratory notification of meningococcal disease is mandatory in Portugal. National database includes since then all confirmed cases notified to the reference laboratory or to the Directorate of Health. Strains included in this study were all the invasive MenB isolated from the 1st July 2011 to the 30th June 2015, sent to the reference laboratory. To predict the vaccine strain coverage of the 4CMenB the expression and cross-reactivity of the surface antigens fHbp, NadA, NHBA were assessed by the Meningococcal Antigen Typing System (MATS) whereas PorA typing was performed by sequencing. The presence of at least one antigen with a Relative Potency (RP) greater than its MATS-positive bactericidal threshold RP value or the presence of PorA VR2 = 4 was considered to be predictive for a strain to be covered by the 4CMenB vaccine.ResultsThe estimated 4CMenB strain coverage in Portugal was 67.9%. The percentage of strain coverage in each of the four epidemiological years ranged from 63.9% to 73.7%.Strains covered by one antigen represent 32.1% of the total of isolates, 29.2% of strains were covered by two antigens and 6.6% by three antigens. No strain had all the four antigens. Antigens that most contributed for coverage were NHBA and fHbp.Data from Portugal is in accordance with the MATS predicted strain coverage in five European countries (England and Wales, France, Germany, Italy and Norway) that pointed to 78% coverage for strains collected in the epidemiological year 2007–2008.
Highlights
Neisseria meningitidis is one of the major causes of bacterial invasive disease worldwide with an estimated 1.2 million cases per year and a mortality rate of about 11% [1]
Data from Portugal is in accordance with the Meningococcal Antigen Typing System (MATS) predicted strain coverage in five European countries (England and Wales, France, Germany, Italy and Norway) that pointed to 78% coverage for strains collected in the epidemiological year 2007–2008
All strains were genotyped according to published protocols: serogroups were identified by PCR [10], serosubtypes were characterized by sequencing of the variable regions VR1 and VR2 of porA gene [10], the outer membrane protein FetA was characterized by sequencing the variable region of fetA gene [11] and multilocus sequence typing (MLST) was done [12] (S1 Table)
Summary
Neisseria meningitidis is one of the major causes of bacterial invasive disease worldwide with an estimated 1.2 million cases per year and a mortality rate of about 11% [1]. Polysaccharide of serogroup B meningococci is a homopolymer of sialic acid residues and has structural similarities to human brain glycoproteins, autoimmune disease could be triggered by its use in vaccines [7] To overcome this challenge, research on vaccines against MenB has been focused on the outer membrane vesicles (OMV) which, very effective, fails in providing broad protection against heterologous MenB strains due to the high variability of the outer membrane antigens, such as porins, present in OMV [8]. This vaccine contains four components: 3 protein antigens that are exposed on the surface of the bacterial cell and are able to elicit antibodies with bactericidal activity, Neisserial Heparin-Binding Antigen (NHBA), factor H binding protein (fHbp), Neisserial Adhesin A (NadA) and the OMV from the epidemic strain NZ98/254 of New Zealand, containing variant P1.4 of the major outer membrane protein PorA [9]
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