The analysis of the potential impact of the meningococcal vaccines in asymptomatic carriers has become one of the key aspects in the evaluation of new vaccines and of their impact on disease control. An important step in this direction is provided by the analysis of the sequence variability and surface-exposure of the 4CMenB (Bexsero®) vaccine antigens, as well as the cross-reactivity of vaccine induced antibodies, in isolates from healthy carriers. The Spanish Reference Laboratory, in collaboration with the University Hospital Marqués de Valdecilla in Santander (Spain), carried out a meningococcal carrier survey between May 2010 and April 2012 (population aged 4 to 19 years). The present study was done on 60 meningococcal carrier strains representative of the overall strain panel obtained and compared to invasive strains isolated in Spain in the same time. We found quantifiable levels of fHbp and NHBA expression and immunologic cross-reactivity in 10% and 75% of analyzed carrier strains, respectively, so the potential impact of the 4CMenB vaccine on Spanish asymptomatic carrier strains is expected to be mediated by the NHBA antigen.