TABLE 4.

Bactericidal activity of combinations of MAbs in relation to the respective locations of the epitopes

JAR MAb pairStrain (variant)Combination BC50, in μg/mlaResidues in epitopesbApprox distancec (Å)fH inhibitiondIg isotypes
5 and 502eH44/76<1G121 and R20416++ and NDG2b and G2a
10 and 118047 (v.2)5K180/E192 and A17418-20− and +G1 and G2a
33 and 32M1239 (v.3)1R180/E192 and K17418-20− and ++G2a and G2a
33 and 35M1239 (v.3)5R180/E192 and K17418-20− and ++G2a and G2b
3 and 10NZ98/254 (v.1)>50G121 and K180/E19231-32++ and −G3 and G1
5 and 10NZ98/254 (v.1)>50G121 and K180/E19231-32++ and −G2b and G1
13 and 35M1239 (v.3)>50S216 and K17427++ and ++G2a and G2b
13 and 118047 (v.2)>50S216 and A17427++ and +G2a and G2a
13 and 32M1239 (v.3)>50S216 and K17427++ and ++G2a and G2a
13 and 33M1239 (v.3)>50S216 and R180/E1929-14++ and −G2a and G2a
13 and 108047 (v.2)>50S216 and K180/E1929-14++ and −G2a and G1
3 and 5NZ98/254 (v.1)>50G121 and G1210++ and ++G3 and G2b
32 and 35M1239 (v.3)>50K174 and K1740++ and ++G2a and G2b
  • a Data are shown only for MAbs that individually were not bactericidal against the test strain (BC50 > 50 μg/ml).

  • b For the respective MAbs in the pair. The numbering of the residues is based on the amino acid sequence of MC58 v.1 fHbp lacking the signal sequence (17).

  • c Distances between the pairs of the MAbs were calculated between alpha-carbon positions for the respective residues using PyMol (http://www.pymol.org). JAR 32 and JAR 35 recognize overlapping (or identical) epitopes including K174.

  • d ++, inhibition of fH binding to rfHbp (>70%); +, partial inhibition (25 to 45%); −, no inhibition (<15%) as measured by ELISA (Fig. 2).

  • e The amino acid affecting the expression of the MAb 502 epitope was described by Giuliani et al. (13). The inhibition of fH binding was not determined (ND).