Mucosal Immunisation with Papillomavirus Virus-like Particles Elicits Systemic and Mucosal Immunity in Mice

Abstract

It has been shown previously that recombinant virus-like particles (VLPs) of papillomavirus can induce VLP-specific humoral and cellular immune responses following parenteral administration. To test whether mucosal administration of bovine papillomavirus type 1 (BPV1) VLPs could produce mucosal as well as systemic immune responses to VLPs, 50 micrograms chimeric BPV1 VLPs containing an HPV16 E7 CTL epitope (BPVL1/E7 VLP) was administered intranasally to mice. After two immunisations, L1-specific serum IgG and IgA were observed. L1-specific IgG and IgA were also found in respiratory and vaginal secretions. Both serum and mucosal antibody inhibited papillomavirus VLP-induced agglutination of RBC, indicating that the antibody induced by mucosal immunisation may recognize conformational determinants associated with virus neutralisation. For comparison, VLPs were given intramuscularly, and systemic and mucosal immune responses were generally comparable following systemic or mucosal delivery. However, intranasal administration of VLP induced significantly higher local IgA response in lung, suggesting that mucosally delivered HPV VLP may be more effective for mediating local mucosal immune responses. Intranasal immunisation with HPV6b L1 VLP produced VLP-specific T proliferative responses in splenocytes, and immunisation with BPVL1 VLP containing an HPV16 E7 CTL epitope induced E7-specific CTL responses. We conclude that immunisation with papillomavirus VLPs via mucosal and intramuscular routes, without adjuvant, can elicit specific antibody at mucosal surfaces and also systemic VLP epitope specific T cell responses. These findings suggest that mucosally delivered VLPs may offer an alternative HPV VLP vaccine strategy for inducing protective humoral immunity to anogenital HPV infection, together with cell-mediated immune responses to eliminate any cells which become infected.

IFN-γ Promotes Generation of IL-10 Secreting CD4+ T Cells that Suppress Generation of CD8 Responses in an Antigen-Experienced Host

“…VLPs were purified from the nuclei of SF9 cells infected with recombinant baculovirus by CsCl gradient centrifugation as previously described (22). Samples were subjected to analysis by transmission electron microscope and immunoblotting to confirm the identity and integrity of the VLPs.…”

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

“…PV VLPs have been used to elicit high titers of systemic neutralizing Abs, which provide protection from experimental challenge with homologous infectious virus in animal PV models (11) and in humans (12). C-terminal truncation mutants of L1 protein also form VLPs, which can elicit immunity to PV and to CTL and B epitopes incorporated at the L1 C terminus, when administered systemically or mucosally (13)(14)(15)(16). PV VLPs have thus been proposed as immunotherapeutic carrier systems (13,15).…”

Lymphotoxin Plays a Crucial Role in the Development and Function of Nasal-Associated Lymphoid Tissue through Regulation of Chemokines and Peripheral Node Addressin

“…3 Similar generation of vaginal IgA was found after intranasal immunization with bovine papillomavirus. 4 The NALT drains into the cervical lymph node (CLN) and that node has been demonstrated to play a role in its activity. 5 Although it was known that cells continued to accumulate in the NALT in the postnatal period, 6,7 scant information was available concerning the kinetics of NALT development, particularly with regard to lymphoid chemokines and vascular adhesion molecules, and the mechanism of the lymphotoxin (LT) family's contribution to postnatal development was unexplored.…”