Long-Term and Memory Immune Responses in Mice against Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus Glycoprotein Ectodomains

Abstract

Although respiratory syncytial virus (RSV) is a significant human pathogen, no RSV vaccines are available. We have reported that a virus-like particle (VLP) RSV vaccine candidate stimulated, in mice, robust, protective anti-RSV glycoprotein T(H)1 biased immune responses without enhanced respiratory disease upon RSV challenge. We report here an analysis of long-term responses to these VLPs. BALB/c mice immunized, without adjuvant, with VLPs or with infectious RSV generated anti-F and anti-G protein serum antibody responses that were stable over 14 months. Neutralizing antibody titers stimulated by VLPs were robust and durable for 14 months, whereas those of RSV-immunized animals declined significantly by 3 months. F protein-specific antibody-secreting cells were detected in the bone marrows of VLP-immunized mice but not in the marrows of RSV-immunized mice. Adoptive transfer of enriched splenic B cells from VLP-immunized mice into immunodeficient rag(-/-) mice resulted in anti-F and anti-G protein serum IgG antibody responses, in recipient mice, that were protective upon RSV challenge. In contrast, transfer of splenic B cells from RSV-immunized mice produced no detectable serum antibody in the recipients, nor could these mice inhibit RSV replication upon virus challenge. Immunization with VLPs stimulated the formation of germinal center GL7(+) B cells in normal mice. VLP immunization of TCR βδ(-/-) T-cell-deficient mice did not induce anti-RSV IgG antibodies, results consistent with T-cell-dependent immune responses. These results demonstrate that VLPs are effective in stimulating long-lived RSV-specific, T-cell-dependent neutralizing antibody-secreting cells and RSV-specific memory responses.