Inability to evoke a long-lasting protective immune response to respiratory syncytial virus infection in mice correlates with ineffective nasal antibody responses

Abstract

Long-lasting protective antibody is not normally generated in children following primary respiratory syncytial virus (RSV) infection, frequently leading to reinfection. We used the BALB/c mouse model to examine the role of the nasal-associated lymphoid tissue and the bone marrow in the generation of RSV-specific long-lasting plasma cells, with a view to further understanding the mechanisms responsible for the poorly sustained RSV antibody levels following primary infection. We show here that substantial numbers of RSV-specific plasma cells were generated in the bone marrow following challenge, which were maintained thereafter. In contrast, in the nasal-associated lymphoid tissue, RSV-specific plasma cell numbers waned quickly both after primary infection and after challenge and were not maintained at a higher level after boosting. These data indicate that the inability to generate a robust local mucosal response in the nasal tissues may contribute substantially to the likelihood of subsequent reinfection and that the presence of serum anti-RSV antibody without local protection is not enough to protect against reinfection.

FIG. 1.

Frequency of RSV-specific AFCs in the O-NALT (A), cervical lymph node (B), and mediastinal lymph node (C) following primary, secondary, and tertiary intranasal infection with respiratory syncytial virus. A minimum of four mice were pooled for each time point. The data show a representative experiment.

FIG. 2.

Frequency of RSV-specific AFCs in the D-NALT (A, C, and E) and the bone marrow (B, D, and F) following primary (A and B), secondary (C and D), and tertiary (E and F) intranasal infection with respiratory syncytial virus. A minimum of four mice were pooled for each time point. The data show a representative experiment.

FIG. 3.

RSV-specific serum IgG subclass responses following primary (A), secondary (B), and tertiary (C) infection with respiratory syncytial virus. Titers were assessed from a minimum of four individual mice per time point. Due to the different titers of the RSV-specific isotypes detected, scaling of the ordinates differs for each isotype.

FIG. 4.

RSV-specific IgG secreted from lung fragments is not long lasting. Secreted antibody from lung fragments was measured at certain time points after primary (A), secondary (B), and tertiary (C) infection with RSV. Four individual mice were assessed per time point. Due to the different titers of the RSV-specific isotypes detected, scaling of the ordinates differs for each isotype.

FIG. 5.

Existing RSV-specific antibody does not protect against secondary or tertiary reinfection of the lung. Lung virus titers were assessed during primary (A), secondary (B), and tertiary (C) infection with RSV. Four individual mice were assessed per time point.