Figure 1.

Rational design of MeV-H Δ8

(A) Model of the dimeric structure of the MeV-H Δ8. N-linked sugars are depicted as brown spheres (N168, N200, N215, and N416). Amino acid differences with regard to the MeV-H vaccine Moraten strain are indicated; red areas are MeV-H-genotype-H1-specific changes, and green areas are engineered nAb escape mutations.

(B) Neutralization sensitivity of viruses encoding MeV-H A, H1, and Δ8 against a panel of 30 mAbs. Boxes are shaded according to differences in log₂ of the antibody concentration required to inhibit viral infection by 50% (neutralizing antibody titer at 50% inhibition [NT₅₀]).

(C) Neutralization sensitivity of viruses encoding genotype-specific MeV-H (A, B3.1, D4.1, D8, G3, and H1; left panel) in comparison with those expressing MeV-H Δ8 or (right panel) MeV-H Δ7 mutants (indicated is the antigenic site still remaining intact) against mouse (black dots) and rabbit (empty dots) sera raised against MeV-H genotype A. A difference of 2 log₂ or more (gray-shaded region) is considered antigenically significant.

(D) MeV glycoprotein-specific antibodies. Shown are IgG antibody levels after incubating MeV-immune human sera from the Dutch cohort with cells expressing MeV-F (condition 3) and comparing their levels with those of untreated human sera (condition 0). Values of less than 30 were considered negative for antibody binding (lower crosshairs).

(E) Neutralization sensitivity of MeV A or Δ8 against MeV-immune human sera after depletion no depletion of MeV-F-specific antibodies. Serum samples were the same as those shown in (D). Each semitransparent line indicates a different individual (n = 6), and the solid trend lines represent the nonlinear regression fitting against MeV A (green) or Δ8 (magenta).

Statistical significance (p < 0.0005) was determined by Wilcoxon matched-pair signed rank test.