AIM: Chimeric papillomavirus virus like particles (PV VLPs) has been proposed as a novel antigen delivery system that combines both antigen and adjuvant properties. I wished to compare their efficacy at inducing systemic and mucosal immune responses after systemic and mucosal delivery.
Methods: (Chapter 2): Various PV L1 chimeric capsid proteins including chimeric BPV1L1 incorporating an HPV16E7 H-2d CTL epitope (L1E7), chimeric BPVL1 incorporating a HIVIIIb P18I10 CTL epitope (L1P18), chimeric BPVL1 VLPs incorporating a HIVIIIb V3 loop polypeptide (L1V3) and a series of chimeric HPV6bLlVLPs incorporating HIV tat, rev and SIV p27 sequences were expressed in a baculovirus expression system. Humoral and cellular immune responses, especially mucosal and systemic responses following various mucosal delivery routes were examined in chimeric PV VLP immunised mice. The immune responses induced by PV VLPs were measured as serum and mucosal antibody responses to LI and incorporated protein, and systemic and local mucosal CTL responses by using 51Cr release assay or the INF-γ secreting ELISPOT assay.
Results: The following observations were made:
1, Chimeric PV VLPs, when delivered mucosally in the absence of any adjuvants, can elicit both mucosal as well as systemic immune responses to PV LI and to incorporated antigenic peptide, although the systemic immune responses are weaker than that from systemic immunised mice (Chapter 4 and chapter 5).
2, Intranasal and intrarectal administration is more effective at inducing mucosal immune responses than intravaginal administration (Chapter 4 and chapter 5).
3, Not all chimeric VLP constructs produce VLPs, however, sub VLP particles can be immunogenic (Chapter 3).
4. Prior immunisation with VLPs affects subsequent responses to new epitopes introduced into the VLPs (Chapter 6).
Conclusions and future directions: From these data it can be concluded that
1, chimeric PV VLPs are a potential vaccine antigen delivery system for inducing both prophylactic and therapeutic immunity to viruses at mucosal surfaces.
2, construction of immunogenic chimeric VLPs remains an empiric technique.
3, prior immunity to VLPs will impact on their utility as a vaccine delivery system. Future studies will explore the molecular and cellular mechanisms ley which prior immunity to VLPs inhibits responses to new epitopes.