NEISSERIA MENINGITIDIS SEROGROUP B CARRIAGE BY ADOLESCENTS AND YOUNG ADULTS LIVING IN MILAN, ITALY: GENETIC CHARACTERISTICS AND POTENTIAL CORRELATION WITH PRESENTLY AVAILABLE MENB VACCINE.

Recently, two vaccines against meningococcal serogroup B have been developed. They are prepared according to the reverse vaccinology approach and contain four and two cross-reactive surface proteins. These vaccines, manufactured by GSK and Pfizer, are Bexsero (4CMenB) and Trumenba (MenB-fHbp) respectively. In Italy Bexsero vaccine has been included in the official vaccination schedule and is recommended for infants, adolescents and adults, whereas Trumenba is recommended for adolescents. In order to collect information about the present carriage of Neisseria meningitidis serogroup B in Italian adolescents and to evaluate the potential protection offered by the presently available MenB vaccines, 2,560 otherwise healthy, high school students aged 14-21 years (907 males, 35.4%, median age 16.2 years) were enrolled in Milan, Italy. A swab to collect posterior pharynx secretions was collected from each subject and meningococcal identification, serogrouping, multilocus sequence typing analysis, sequence alignments and phylogenetic analysis were performed. A total of 135 (5.3%) adolescents were meningococcal carriers. Strains belonging to serogroup B were the most common (n = 58; 43%), followed by MenY (n = 32; 23.7%), MenC (n = 7; 5.2%), MenW135 (n = 6; 4.4%) and MenX (n = 5; 3.7%). The remaining bacteria were not capsulated. The identified MenB strains belonged to eleven clonal complexes (CCs): ST-162 CC (n = 12; 20.7%), ST-865 CC (n = 12; 20.7%), ST-41/44/Lin.3 CC (n = 11; 19.0%), ST-35 CC (n = 6; 10.3%), ST-32/ET-5 CC (n = 4; 6.9%), ST-269 CC (n = 3; 5.2%), ST-213 CC (n = 2; 3.4%), ST-198 CC (n = 1; 1.7%), ST-461 CC (n = 1; 1.7%), ST-549 CC (n = 1; 1.7%), and ST-750 CC (n = 1; 1.7%). The analysis of proteins included in two vaccines show that, regarding fHbp gene, all strains except 3 harbored fHbp alleles represented by a total of 31 sub-variants: 18 in variant 1 (v.1 n=25; 45.4%), 8 in variant 2 (v.2 n=25; 45.4%) and 5 in variant 3 (v.3, n=5; 9.1%). The data concerning the percentage of amino acid identity shows that for the detected fHbp sub-variants 1 the identity towards Bexsero varies from 90.9% to 99.2% (median: 96.1%) instead against Trumenba varies from 87.7% to 93.1% (median: 89.2%). The identity regarding detected sub-variant 3 towards the MenB fHbp varies from 93.7% to 100% (median 97.6%). The gene for NHBA protein was found in all strains except for 6 (10.3%) and 21 sub-variants were identified. The sub-variants had an amino acid identity towards the protein included in the Bexsero varying from 71.3% to 99.8% (median: 76%). PorA gene were identified in 53 out of the 58 (91.4%) studied MenB strains and 22 porA sub-types were identified. The amino acid identity between the studied porA proteins and those were included in the Bexsero vaccine was not less than 88.1% (median: 91.8%). The gene for NadA proteins was not detected in any of the 58 studied strains, as expected in carried strains. In conclusion, in adolescent living in Milan, Neisseria meningitidis serogroup B was the most commonly carried followed by serogroup Y. The MenB vaccines presently licensed induce the production of antibodies effective against the greatest part of the identified MenB strains. Monitoring carriage remains essential to evaluate MenB circulation and long-term studies will be useful to evaluate the effects on the carriage and the final efficacy of both new MenB vaccines.