Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection

Abstract

We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 ؋ 10 10 and 2 ؋ 10 11 particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection. Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme-linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection.

Virus-like particle-based vaccines for animal viral infections

“…87 Induction of a protective immune response was also previously reported in cattle (reviewed in Ref. 88), rabbits (cottontail rabbit papillomavirus, CRPV) 89 and dogs (canine oral papillomavirus). 90…”

Expression, purification and characterization of enterovirus-71 virus-like particles

“…These data suggest that the VLPs contain the important antigenic sites essential for eliciting the immune responses. This is particularly impor tant because neutralizing epitopes are most densely clustered on VP1 and many of them consist of amino acids from different domains or from different polypeptides [36,37] , that is, many of them are conformationdependent. In this regard, the use of VLP as a vaccine candidate against EV71 infection may be particularly promising.…”

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

“…There is also a minor capsid protein involved in the capsid structure; its exact interaction and location in relation to L1 have not been fully characterised; however, it is proposed that the ratio of L1 to L2 is 30:1 [20]. Immunization with self-assembled VLPs made up of L1 or L1 and L2 induces neutralizing antibodies that confer type-specific and long-lasting protection in 3 different animal models of papillomavirus infection [2,21,34]. In recent years, considerable progress has been made towards the development of prophylactic human papillomavirus (HPV) vaccines to prevent genital HPV infections [17,45], and evidence of clinical protection has recently been demonstrated [16,22].…”