Showing papers by "John J. Donnelly published in 1996"

Generation of MHC class I-restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non-muscle cells.

Abstract: Expression of reporter genes in muscle cells has been achieved by intramuscular (i.m.) injection of plasmid DNA expression vectors. We previously demonstrated that this technique is an effective means of immunization to elicit both antibodies capable of conferring homologous protection and cell-mediated immunity leading to cross-strain protection against influenza virus challenge in mice. These results suggested that expression of viral proteins by muscle cells can result in the generation of cellular immune responses, including cytotoxic T lymphocytes (CTL). However, because DNA has the potential to be internalized and expressed by other cell types, we sought to determine whether or not induction of CTL required synthesis of antigen in non-muscle cells and, if not, whether transfer of antigen to antigen-presenting cells from muscle cells may be involved. In the present study, we demonstrate that transplantation of nucleoprotein (NP)-transfected myoblasts into syngeneic mice led to the generation of NP-specific antibodies and CTL, and cross-strain protective immunity against a lethal challenge with influenza virus. Furthermore, transplantation of NP-expressing myoblasts (H-2k) intraperitoneally into F1 hybrid mice (H-2d × H-2k) elicited NP CTL restricted by the MHC haplotype of both parental strains. These results indicate that NP expression by muscle cells after transplantation was sufficient to generate protective cell-mediated immunity, and that induction of the CTL response was mediated, at least in part, by transfer of antigen from the transplanted muscle cells to a host cell.

Protection against Papillomavirus with a Polynucleotide Vaccine

Abstract: Genital infectionswith human papillomavirus(HPV) are increasingly recognized as a significant source of human disease; HPV is now implicated in up to 90% of cervicalcarcinomas.Neutralizing antibodies against papillomaviruses recognize conformational epitopes formed when viral capsid proteins assemble into virions or virus-like particles. Immunization with plasmid DNA encoding the major viral capsid protein L1 was studied as a means of inducing neutralizing antibodies and protection against virus challenge. In a cottontail rabbit papillomavirus (CRPV) model, immuniza­ tion with plasmid DNA encoding L1 elicitedconformationally specific neutralizing antibodies and provided immunity against papilloma formation upon challenge with CRPV. Immunization with DNA encoding the capsid protein may provide a means of protecting humans against HPV and would simplifythe production of multivalent vaccines by combining plasmids that encode the viral capsid proteins of different strains. This may be of importance given the multiplicity of HPV types capable of causing disease. Genital infection with human papillomavirus (HPV) is in­ creasingly recognized as a source of sexually transmitted dis­ ease in the United States [1], Infection with HPV may cause genital condylomas and cervical neoplasia and may be associ­ ated with as many as 90% of cervical carcinomas [2]. There are at least 76 types of HPV, and -40 infect the human repro­ ductive tract [3]. Types 16, 18, 31, 33, 35, 45, and 56 are commonly found in premalignant dysplasias and cervical carci­ nomas and are thought to be etiologic agents for cancer, whereas types 6, 11, 42, 43, and 44 are the most common causes of genital condylomas [3]. Both the carcinoma- and condyloma-associated types may be found in cervical intraepi­ thelial neoplasia [3].