FIG. 7.

Assessment of vaccine potential of triple mutants by immunization of mice with either KR/EG/DE or KR/EG/PM and subsequent challenge with CVB3(T7). The histology of the heart and the pancreas on days 3, 10, and 28 postchallenge is shown. Mice that were immunized with either triple mutant showed no tissue damage following challenge with 10⁶ PFU of CVB3(T7) on day 21 postimmunization, either on day 3 when pancreatic damage is maximal or on day 10 when fibrosis of the heart is normally extensive. In contrast, widespread damage was seen in mice that had been inoculated with PBS and then challenged with equivalent amounts of wt virus (b, c, k, and l). (a) Control pancreas. (b) CVB3(T7) infection on day 3 p.i. Massive acinar necrosis (N.Ac) and a condensed islet (I) are present. (c) CVB3(T7) infection on day 10 p.i. Acinar necrosis and substantial lymphocytic infiltration are present. (d to f) CVB3(DE) triple mutant infection on days 3, 10, and 28 p.i. The pancreas is intact and no necrosis is visible. (g to i) CVB3(PM) triple mutant infection on days 3, 10, and 28 p.i. No damage to acinar tissue or islets is visible. (j) Control heart. (k) CVB3(T7) infection on day 3 p.i. Foci of acute viral damage and cell necrosis are indicated with arrows. (l) CVB3(T7) infection on day 10 p.i. Large areas of fibrosis are present (arrows). (m to o) CVB3 (DE) triple mutant infection on day 3, day 10, and day 28 p.i. No heart damage is present. (p to r) CVB3(PM) triple mutant infection on day 3, day 10, and day 28 p.i. No heart damage is present.