The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine

Background. One of the promising avenues for development of vaccines against Human immunodeficiency virus type 1 (HIV-1) and other human pathogens is the use of plasmid-based DNA vaccines. However, relatively large doses of plasmid must be injected for a relatively weak response. We investigated whether genome elements from Porcine circovirus type 1 (PCV-1), an apathogenic small ssDNA-containing virus, had useful expression-enhancing properties that could allow dose-sparing in a plasmid vaccine. Results. The linearised PCV-1 genome inserted 5' of the CMV promoter in the well-characterised HIV-1 plasmid vaccine pTHgrttnC increased expression of the polyantigen up to 2-fold, and elicited 3-fold higher CTL responses in mice at 10-fold lower doses than unmodified pTHgrttnC. The PCV-1 capsid gene promoter (Pcap) alone was equally effective. Enhancing activity was traced to a putative composite host transcription factor binding site and a "Conserved Late Element" transcription-enhancing sequence previously unidentified in circoviruses. Conclusions. We identified a novel PCV-1 genome-derived enhancer sequence that significantly increased antigen expression from plasmids in in vitro assays, and improved immunogenicity in mice of the HIV-1 subtype C vaccine plasmid, pTHgrttnC. This should allow significant dose sparing of, or increased responses to, this and other plasmid-based vaccines. We also report investigations of the potential of other circovirus-derived sequences to be similarly used. © 2011 Tanzer et al; licensee BioMed Central Ltd

Production and immunogenicity of chimaeric human papillomavirus-like particle vaccines

Includes bibliographical references (leaves 129-146).Human papillomavirus (HPV) infection, specifically with oncogenic types, has been implicated in effectively all cervical cancer cases. Cervical cancer is a global health burden, especially in the developing world. Up to 18 types of HPV are considered oncogenic, of which HPV -16 and -18 cause 70% of cervical cancer cases worldwide. Two vaccines are available on the market: Gardasil(R), targeted against HPV -16, -18; -6 and -11, and Cervarix(TM), against -16 and -18. Both vaccines are based on the L1 capsid proteins of the types they are targeted to and are efficient, pro- phylactic, typespecific vaccines. However, two problems remain: they do not protect against nonvaccine types, that may cause a significant proportion of cancers specifically in African and HIV- positive populations, and they cannot be used to treat existing infections. We designed eight different chimaeric vaccines