Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in respiratory syncytial virus (RSV)-challenged naive and formalin-inactivated RSV-immunized BALB/c mice

Abstract

We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab')(2) forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.

FIG. 1.

Effect of MAb 131-2G prophylaxis on pulmonary leukocyte trafficking and RSV titers after primary RSV infection. (A) The mean BAL fluid cell numbers (±standard errors) in the lungs of antibody-treated (nIg or anti-G MAb) RSV-infected mice. (B) Virus titers (PFU/g of tissue; ±standard errors) in the lungs of RSV-infected mice. (C) Real-time RT-PCR M gene expression in the lungs of antibody-treated mice. e, equivalent. (D) IFN-γ levels (±standard errors) in cell-free BAL fluid. Results are representative of three independent experiments with no fewer than three mice per time point. Asterisks indicate a significant difference (P < 0.05) between nIg-treated and antibody-treated mice. N/D indicates virus titers below the level of detection.

FIG. 2.

Effect of MAb 131-2G prophylaxis on illness in FI-RSV-vaccinated mice. (A) Mean BAL cell numbers (±standard errors) in the lungs of FI-RSV-vaccinated mice treated with either nIg or MAb 131-2G. The data are representative of three independent experiments examining four mice per treatment. The asterisk indicates a significant difference (P < 0.05) between nIg-treated and antibody-treated mice. (B) Percent initial body weight (±standard error) of nIg- or MAb 131-2G (anti-G MAb)-treated FI-RSV-vaccinated mice after RSV challenge.

FIG. 3.

Effect of MAb 131-2G F(ab′)₂ prophylaxis on illness in FI-RSV-vaccinated mice. (A) Mean BAL fluid cell numbers (±standard errors) in the lungs of nIg-, MAb 131-2G (anti-G MAb)-, or 131-2G F(ab′)₂ fragment [anti-G F(ab′)₂]-treated FI-RSV-immunized mice after RSV challenge. (B) Percentages of eosinophils, as determined by hematoxylin and eosin staining and microscopic analysis (±standard errors), in the lungs of treated FI-RSV-vaccinated mice after RSV challenge. (C) IL-4 levels (±standard errors) in cell-free BAL fluid supernatants from mice on days 3, 5, and 7 after RSV challenge. Representative data from three independent experiments examining four mice per treatment are shown. Asterisks indicate a significant difference (P < 0.05) in comparison to nIg-treated mice as determined by Student's t test.