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Induction of mucosal B-cell memory by intranasal immunization of mice with respiratory syncytial virus - PubMed

Comparative Study

Induction of mucosal B-cell memory by intranasal immunization of mice with respiratory syncytial virus

Janine Valosky et al. Clin Diagn Lab Immunol. 2005 Jan.

Abstract

The capacity of live or inactivated respiratory syncytial virus (RSV) to induce B-cell memory in respiratory-associated lymphoid tissues of mice was examined. Eight weeks after primary inoculation with either live or inactivated RSV, adult BALB/c mice were challenged with 4x10(5) PFU of RSV. Protection from viral shedding and mucosal production of RSV-specific antibodies were examined at various time points after challenge. We found that primary immunization with live, but not inactivated, RSV induced complete and durable protection upon challenge within the upper and lower respiratory tract. Also, primary immunization with live, but not inactivated, RSV enhanced the production of mucosal RSV-specific immunoglobulin A (IgA) upon challenge. Secondary mucosal IgA responses were characterized by (i) the early production of mucosal IgA by B cells that reside in organized nasal-associated lymphoid tissues, cervical lymph nodes, and bronchial lymph nodes, and (ii) the subsequent production of RSV-specific IgA by mucosal effector tissues, such as the tracheal lamina propria and lung. These findings suggest that primary infection of mice with live RSV might induce mucosal IgA-committed memory B cells. A greater understanding of the characteristics of RSA-specific mucosal memory B cells may facilitate the development of an RSV vaccine.

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Figures

FIG. 1.
FIG. 1.

Eight and 59 weeks after primary i.n. immunization with live RSV, iRSV, or medium, five adult BALB/c mice per group per time point were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. Nasal washes, BAL fluid, and processed lung samples were tested to determine the quantities of PFU of RSV in each sample. Viral titrations were determined by plaque assay. Geometric means were calculated. *, P < 0.05 compared to quantities of virus detected in samples from control mice; all other differences were not statistically significant (P > 0.05).

FIG. 2.
FIG. 2.

Eight weeks after primary i.n. immunization with live RSV, iRSV, or medium, five adult BALB/c mice per group per time point were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. (A) Inductive tissues (NALT, CLN, and BLN) (A) and effector tissues (SM, tracheal lamina propria, and lung) (B) were isolated and cultured. The quantities of RSV-specific IgA produced were determined by ELISA 0, 3, 6, and 9 days after challenge. Data represent the arithmetic mean and standard error of the mean of the percentage of RSV-specific IgA compared to the total IgA produced. *, P < 0.05 compared to the percentage of RSV-specific IgA in samples from control mice; all other differences were not statistically significant (P > 0.05).

FIG. 3.
FIG. 3.

Eight weeks after primary i.n. immunization with live RSV, iRSV, or medium, five adult BALB/c mice per group per time point were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. Inductive tissues (NALT, CLN, and BLN) (A) and effector tissues (SM, tracheal lamina propria, and lung) (B) were isolated and cultured. The quantities of RSV-specific IgG produced were determined by ELISA 0, 3, 6, and 9 days after challenge. Data represent the arithmetic mean and standard error of the mean of the percentage of RSV-specific IgG compared to the total IgG produced. *, P < 0.05 compared to the percentage of RSV-specific IgG in samples from control mice; all other differences were not statistically significant (P > 0.05).

FIG. 4.
FIG. 4.

Eight weeks after primary i.n. immunization with live RSV, iRSV, or medium, five adult BALB/c mice per group per time point were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. Nasal washes, BAL fluid, and processed lung samples were tested to determine the quantities of RSV-specific IgA (A) or RSV-specific IgG (B) produced by ELISA 0, 3, 6, and 9 days after challenge. Graphed data represent the arithmetic mean and standard error of the mean of the percentage of RSV-specific antibodies compared to the total antibodies produced. Tables report the mean quantities of RSV-specific antibodies versus total antibodies.

FIG. 5.
FIG. 5.

At 59 weeks after primary i.n. immunization, lymphoid fragment cultures of four to five adult BALB/c mice per group were established. In addition, four to five previously immunized mice were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. Six days after challenge, lymphoid fragment cultures were established. The quantities of RSV-specific IgA produced were determined by ELISA 0 and 6 days after challenge. Data represent the arithmetic mean and standard error of the mean of the percentage of RSV-specific IgA compared to the total IgA produced.

FIG. 6.
FIG. 6.

At 59 weeks after primary i.n. immunization, lymphoid fragment cultures of four to five adult BALB/c mice per group were established. In addition, four to five previously immunized mice were challenged i.n. with 20 μl containing 4 × 105 PFU of RSV. Six days after challenge, lymphoid fragment cultures were established. The quantities of RSV-specific IgG produced were determined by ELISA 0 and 6 days after challenge. Data represent the arithmetic mean and standard error of the mean of the percentage of RSV-specific IgG compared to the total IgG produced.

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