Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16

Davies, Daniel; Hill, Charles H.; Rothbard, Jonathan B.; Chain, Benjamin M.

doi:10.1099/0022-1317-71-11-2691

Cited by 15 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A major obstacle in studying CMI to HPV is the lack of a suitable culture system to propagate the virus in vitro. As a result, several investigators have used synthetic peptides de-rived from HPV type 16 (HPV-16) sequences (1,8,9,13,19,32,34,36) as well as recombinant viruses expressing HPV-16 genes (13,39) as sources of antigens for CMI assays. In this study, we used one of the commonly studied measures of CMI response, TCP response, to investigate its association with respect to detection of HPV infection and to HPV-related cervical disease.…”

mentioning

confidence: 99%

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia

Nakagawa

Stites

Farhat

et al. 1996

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

The incidence of human papillomavirus (HPV)-related cervical intraepithelial neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the role of immune response, including cell-mediated immunity, in disease prevention is not well understood. In this study, T-cell proliferative responses to six synthetic peptides with predicted immunogenic determinants from the HPV-16 E4, E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with new-onset CIN and 65 sexually active women without cervical disease, characterized by cytology, colposcopy, and HPV testing. T-cell proliferative responses were demonstrated to all six HPV-16 peptides. Although not statistically significant, rates of reactivity to E6 (24-45) were higher among sexually active women without disease (26%) than among women with current CIN (7%), as was the overall number of peptides stimulating a response. Women with CIN may not respond to selected HPV antigens as well as women without disease do.

show abstract

mentioning

confidence: 99%

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia

Nakagawa

Stites

Farhat

et al. 1996

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

show abstract

“…There is limited information on T cell responses to HPV-16 (Stranget al, 1990;Davies et al, 1990), although two groups have recently reported the response of mice to the HPV-16 E7 protein Tindle et al, 1991). The E7 molecule is important because of its proposed involvement in cellular transformation in tissue culture (Matlashewski et al, 1987;Phelps et al, 1988) and because its gene is found integrated into the DNA of a high proportion of carcinomas in which HPV DNA is present (Diirst et al, 1983;Gissmann et al, 1983Gissmann et al, , 1984.…”

mentioning

confidence: 99%

T cell responses to the human papillomavirus type 16 E7 protein in mice of different haplotypes

Shepherd¹,

Tran²,

Rowe³

et al. 1992

Journal of General Virology

View full text Add to dashboard Cite

The response of murine T cells to the E7 molecule of human papillomavirus type 16 (HPV-16) was studied using eight different mouse strains of six distinct H-2 haplotypes. HPV-16 E7 protein was prepared as a fusion protein with glutathione-S-transferase, purified by affinity chromatography and used for immunization. Cells from the lymph nodes were cultured with whole fusion protein, glutathione-S-transferase or HPV-16 E7 protein synthetic peptides. All the mouse strains tested, with the exception of BALB/c, recognized the E7 molecule, as evidenced by a proliferative response to at least two of the peptides. The profile of responses to peptides varied between and within a strain, but five distinct immunodominant regions could be identified. These regions were defined on the basis of a reaction to one or more peptides in a given part of the E7 molecule by at least four strains. The five regions were encompassed by amino acid residues 1 to 9, 17 to 32, 42 to 59, 62 to 77 and 87 to 98. The findings suggest that in an outbred population, such as man, the E7 molecule of HPV-16 would be recognized by a large proportion of the population. However, the poor response of two mouse strains [B10.RIII (71NS) and BALB/c] could also have a corollary in man.Certain human papillomavirus (HPV) types have been implicated in the aetiology of benign and malignant lesions of the ano-genital region. We are interested in identifying immune responses to one of the more important HPV types, namely HPV-16. Little is known about the immunobiology of HPV-16 because the virus cannot easily be grown in vitro or in vivo, and few virions can be isolated from genital lesions. To circumvent these problems, both early and late regions of the HPV-16 genome have been expressed as bacterial fusion proteins (Jenison et al., 1989;Jochmus-Kudielka et al., 1989).

show abstract

“…Although papillomavirus VLPs have been shown to assemble in diverse eukaryotic cell types (7,8,12,14,34,36), assembly has not previously been demonstrated in prokaryotes. L1 fusion proteins have mainly been expressed in bacteria (1,11,15,31), and when bona fide L1 proteins were expressed, VLP assembly was not examined (5). In this study, we have demonstrated that HPV16 VLPs do assemble in Salmonella, probably because of the high-level expression of wild-type L1 and because neither glycosylation of L1 nor eukaryotic chaperons are required for capsid assembly (46).…”

Section: Discussionmentioning

confidence: 84%

Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice

et al. 1997

View full text Add to dashboard Cite

Attenuated strains of Salmonella are attractive live vaccine candidates for eliciting mucosal as well as systemic immune responses. The ability to induce immune responses in the reproductive tract may be critical for the effectiveness of a prophylactic vaccine against genital human papillomaviruses (HPV), which are important etiologic agents in the development of cervical cancer. To examine the potential of a live Salmonellabased vaccine to prevent genital HPV infection, the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed in the PhoP c strain of Salmonella typhimurium. As demonstrated by electron microscopy, the L1 protein expressed in these bacteria assembled into virus-like particles (VLPs) that resemble authentic papillomavirus virions. This is the first demonstration that papillomavirus VLPs can self-assemble in prokaryotes. BALB/c mice were immunized with the HPV16 L1 recombinant PhoP c strain by the oral and nasal routes. Despite a low stability of the L1-expressing plasmid in vivo, a double nasal immunization was effective in inducing L1-specific serum antibodies that recognized mainly native, but not disassembled, VLPs. These antibodies effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were also detected in oral and vaginal secretions, indicating that potentially protective antibody responses were elicited at mucosal sites. Recombinant attenuated Salmonella expressing HPV capsids may represent a promising vaccine candidate against genital HPV infection.

show abstract

Definition of murine T helper cell determinants in the major capsid protein of human papillomavirus type 16

Cited by 15 publications

References 35 publications

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia

T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia

T cell responses to the human papillomavirus type 16 E7 protein in mice of different haplotypes

Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice

Contact Info

Product

Resources

About