Vaccine-enhanced disease is not observed with rgRSV mutants. Lung histopathology from the cotton rats immunized with 500 PFU of the rgRSV mutant viruses or PBS, denoted BUF, (followed by challenge at 28 dpi with RSV A2 and sacrifice 4 days later) was analyzed and compared with historical controls from a previous FI-RSV study. (A) The severity of alveolitis in each cotton rat was graded based on the extent of parenchyma affected (grade 0, 0% affected, within normal limits; grade 0.5, <5% affected; grade 1, <10% affected; grade 2, 10% to 25% affected; grade 3, 25% to 50% affected; grade 4, >50% affected) (51). (B) Representative photomicrographs depicting neutrophilic infiltrates in the alveolar spaces or lack thereof (magnification, ×60). rgRSV-immunized groups were compared to historical controls immunized with FI-RSV, challenged at 28 dpi, and sacrificed at 5 dpc. For the alveolitis scoring, the median alveolitis score from the five cotton rats is shown, with dots representing the individual scores. Statistical significance was determined by a one-way analysis of variance (ANOVA) with Dunnett’s post hoc test for individual comparisons. ns, not significant; ****, P < 0.001.