A total of 73 invasive MenW:cc11 isolates from England and Wales were received by the Public Health England Meningococcal Reference Unit during July 2010–June 2013. These isolates were queried within the Meningitis Research Foundation Meningococcus Genome Library (http://pubmlst.org/perl/bigsdb/bigsdb.pl?db = pubmlst_neisseria_mrfgenomes) for nadA and nhba and, where present, their respective allelic and peptide variants.

We used an SBA using human complement (hSBA) against 6 invasive MenW:cc11 isolates from patients 4 months–91 years of age in whom meningitis or septicemia was diagnosed in different regions of England and Wales during 2011–2012. SBA titers were expressed as the reciprocal of the serum dilution corresponding to >50% bacterial killing. We used pooled serum samples from phase 2 clinical trials involving infants immunized with Bexsero at 2, 3, and 4 months or 2, 4, and 6 months and after administration of a booster at 12, 18, or 24 months (8). Pooled prevaccination serum samples from 180 infants were used as negative controls, and pooled serum samples from 10 randomly selected adolescents who received a single MenACWY conjugate vaccine (GSK Vaccines) dose as positive controls.

Of the 6 isolates tested, 4 possessed nadA allele 5 (for peptide NadA-2/3.6) and nhba allele 17 (for NHBA peptide 29). Of the remaining 2 isolates, 1 isolate had a nadA allele (allele 146) that differed at a single nucleotide (C476A), causing a single amino acid change (T159K; peptide NadA-2/3.130); the other isolate had an nhba allele (allele 72) that differed at a single nucleotide (A376C), causing a single amino acid change (T126P; peptide 96).

hSBA titers were high and were >1:32 against all 6 MenW isolates, independently of the immunization schedule (Table). After the booster, higher hSBA titers were obtained than those from primary immunization, and similar responses were comparable to those among adolescents who had received a single MenACWY dose. Preimmunization serum samples showed no detectable hSBA titers against any of the 6 isolates (Table).

The ability of the antibodies raised by Bexsero antigens to induce SBA activity against any given meningococcal isolate depends on the presence, level of surface expression, and sequence diversity of the respective antigens. Bexsero strain coverage can be predicted by using the Meningococcal Antigen Typing System, an ELISA which measures the level of antigen expression and antigenic diversity compared with the antigen in the vaccine (9). However, the correlation between the relative potency estimated by this typing system and the ability of a meningococcal isolate to be killed by serum from immunized persons has only been defined for MenB strains.

We found that MenW:cc11 isolates causing invasive disease in England and Wales possessed alleles for NadA-2/3 peptide variants that are predicted to be highly cross-protective with the Bexsero NadA variant (10). The isolates also possessed alleles for NHBA peptide 29 which, although different from peptide 2 in Bexsero, has the potential to induce cross-protection even if NHBA-containing cross-protective epitopes have not been defined yet. Antibodies against Bexsero antigens can act synergistically and, therefore, the complement-mediated bactericidal killing observed could be mediated by antibodies against NadA, NHBA, or both.

Figure

Figure. Age distribution of all laboratory-confirmed, invasive Neisseria meningitidis serogroup W disease cases identified in England during July 2009–December 2014.

In England, the ongoing MenW increase is similar to the MenC:cc11 outbreak in the mid-1990s, which was eventually controlled through mass vaccination (11). The increase in MenW cases has led to the rapid introduction of a national adolescent MenACWY conjugate vaccination program in August 2015 (https://www.gov.uk/government/news/new-meningococcal-vaccination-programme-expected-to-save-lives). In adolescents, a single MenACWY dose would provide direct protection and, by targeting the age group most likely to carry meningococci (12), could also provide indirect protection against MenW (Figure) and the other 3 capsular groups by reducing carriage and onward transmission to others.

Conversely, infants would require >2 MenACWY doses starting at 2 months of age, because MenW cases increase from birth and peak at 7 months of age before declining. Bexsero, which is predicted to protect against 73%–88% of invasive MenB isolates in England and Wales (9,13), could offer additional protection against MenB, which causes more cases among infants and toddlers than the other meningococcal serogroups. Among infants (<1 year of age), 101 MenB cases were reported during 2014–2015, compared with 21 MenW, 4 MenY, and 1 MenC; among toddlers, (1–4 years of age), 139 MenB cases were reported, compared with 18 MenW, 5 MenY, and 0 MenC. The difference in adolescents (15–19 years of age) is less pronounced, but 36 MenB cases were reported in this age group during 2014–2015, compared with 25 MenW, 14 MenY and 3 MenC cases (https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/476989/hpr38-3915.pdf). However, the effectiveness of Bexsero against meningococcal carriage and, therefore, its ability to provide herd protection, which is a major objective of an adolescent programme, is less certain than with conjugate vaccines (14). These observations and our results support the recent implementation of both the adolescent MenACWY conjugate and infant MenB immunization programmes in the UK.