Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

Product review on the IMD serogroup B vaccine Bexsero®.

Bexsero® is a multicomponent vaccine composed of four major proteins of Neisseria meningitidis: the fHbp, NHBA, NadA and PorA. This vaccine was licensed against invasive meningococcal disease (IMD) due to serogroup B isolates. When administered alone, Bexsero® showed a safety profile similar to other childhood vaccines. It provides an excellent immunogenicity but that requires booster doses in infants and young children. Although the vaccine does not seem to impact on acquisition of carriage of serogroup B isolates, it confers protection against isolates of serogroup B harboring distinct but cross-reactive variants of fHbp, NadA and NHBA. Primary vaccination schemes in infancy underwent a rapid increase after a toddler booster suggesting an anamnestic response and the establishment of a memory response. As Bexsero® targets sub-capsular proteins that can be conserved regardless the capsule, the vaccine can be effective against non-B isolates such as isolates of serogroups W and X.

Correlates of protection for meningococcal surface protein vaccines: lessons from the past.

INTRODUCTION: Recombinant surface protein meningococcal serogroup B (MenB) vaccines are available but with different antigen compositions, leading to differences between vaccines in their immunogenicity and likely breadth of coverage. The serology and breadth of coverage assessment for MenB vaccines are multifaceted areas, and a comprehensive understanding of these complexities is required to appropriately compare licensed vaccines and those under development. AREAS COVERED: In the first of two companion papers that comprehensively review the serology and breadth of coverage assessment for MenB vaccines, the history of early meningococcal vaccines is considered in this narrative review to identify transferable lessons applicable to the currently licensed MenB vaccines and those under development, as well as their serology. EXPERT OPINION: Understanding correlates of protection and the breadth of coverage assessment for meningococcal surface protein vaccines is significantly more complex than that for capsular polysaccharide vaccines. Determination and understanding of the breadth of coverage of surface protein vaccines are clinically important and unique to each vaccine formulation. It is essential to estimate the proportion of MenB cases that are preventable by a specific vaccine to assess its overall potential impact and to compare the benefits and limitations of different vaccines in preventing invasive meningococcal disease.

Durability of immunogenicity and strain coverage of MenBvac, a meningococcal vaccine based on outer membrane vesicles: Lessons of the Normandy campaign.

OBJECTIVES: MenBvac® is an outer membrane vesicle (OMV)-based meningococcal vaccine. From 2006 to 2012, it was used to control a clonal B outbreak in Normandy (France). We aimed to analyse the durability of the response against the epidemic strain and coverage beyond the vaccine strain. These data should help to optimize the use of OMV-containing vaccines, such as the new 4CMenB/Bexsero® recombinant vaccine. METHODS: Serum bactericidal activity (SBA) was measured in two cohorts of children who received their first dose of MenBvac® at 1-5years of age and accepted to provide a blood sample either one or four years after a 2+1+1 schedule. All sera were tested against the outbreak strain. Sera from responder subjects were also tested against 12 additional B or C strains which were chosen to entirely, partially, or not at all match the two variable regions (VR1 and VR2) of the PorA vaccine strain. RESULTS: Only 47.9% and 31.3% of subjects showed an SBA titre consistent with protection one and four years, respectively, after the last boost. Protective SBA titres were observed in all sera against B or C strains that entirely matched P1.7,16, and was high (75-100%) for all but one strain that partially matched VR1 or VR2. Extrapolating our data to the OMV component of 4CMenB/Bexsero® suggests that 14.5% of the current B strains would be covered based on PorA matching to the OMV component of 4CMenB/Bexsero® (regardless of the coverage of the three other vaccine components). CONCLUSIONS: Our data confirm that OMV-based vaccines elicit short-lasting SBA titres and may require repeated booster injections. However, strain coverage may be greater than expected.

Impact of MenBvac, an outer membrane vesicle (OMV) vaccine, on the meningococcal carriage.

The aim of the study was to analyze the impact of MenBvac, an outer membrane vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were randomly selected to participate in the study. Among the 1082 volunteers, there were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac vaccination appeared associated with lower carriage rate, i.e., 0.31% among the vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The beneficial effect on carriage was observed regardless of the strain serogroup. OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog and hererolog strains in respiratory pathways after intranasal challenge. These results suggest that meningococcal OMV-based vaccines reduce meningococcal carriage and may hence confer herd immunity.

The concept of "tailor-made", protein-based, outer membrane vesicle vaccines against meningococcal disease.

Protein-based, outer membrane vesicle (OMV) vaccines have previously proven to be efficacious against serogroup B meningococcal disease in Norway and Cuba. Currently, a public health intervention is going on in order to control a serogroup B epidemic in New Zealand. The scale-up and standardization of vaccine production required for controlling the New Zealand epidemic has allowed the establishment of large-scale GMP manufacturing for OMV vaccines. The outcome of this will be licensing of the vaccine in New Zealand and possibly other countries. The availability of licensed OMV vaccines raises the question of whether such vaccines may provide the opportunity to control other outbreaks and epidemics. For instance, such a vaccine could control a localised outbreak of group B meningococci in Normandy, France. "Tailor-made" vaccines, focusing on the sub-capsular antigens may also be considered for use in sub-Saharan Africa for the prevention of the recurrent outbreaks by serogroups A and W135 meningococci. This assumption is based on the epidemiological observation that meningococcal outbreaks in Africa are clonal and are strikingly stable regarding their phenotypic characteristics.