scholarly journals The Nature of the Attenuation of Salmonella typhimurium Strains Expressing Human Papillomavirus Type 16 Virus-Like Particles Determines the Systemic and Mucosal Antibody Responses in Nasally Immunized Mice

1999 ◽  
Vol 67 (7) ◽  
pp. 3674-3679 ◽  
Author(s):  
Jalil Benyacoub ◽  
Sally Hopkins ◽  
Alexandra Potts ◽  
Sandra Kelly ◽  
Jean-Pierre Kraehenbuhl ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Salmonella Typhimurium ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Core Antigen ◽  
Human Papillomavirus Type 16 ◽  
Mucosal Antibody ◽  
Nasal Immunization ◽  
Hepatitis B Core Antigen

ABSTRACT We have recently shown by using a recombinant Salmonella typhimurium PhoPc strain in mice the feasibility of using a Salmonella-based vaccine to prevent infection by the genital human papillomavirus type 16 (HPV16). Here, we compare the HPV16-specific antibody responses elicited by nasal immunization with recombinant S. typhimurium strains harboring attenuations that, in contrast to PhoPc, are suitable for human use. For this purpose, χ4989 (Δcya Δcrp) and χ4990 [Δcya Δ(crp-cdt)] were constructed in the ATCC 14028 genetic background, and comparison was made with the isogenic PhoPc and PhoP− strains. Although the levels of expression of HPV16 virus-like particle (VLP) were similar in all strains, only PhoPc HPV16 induced sustained specific antibody responses after nasal immunization, while all strains induced high antibody responses with a single nasal immunization when an unrelated viral hepatitis B core antigen was expressed. The level of the specific antibody responses induced did not correlate with the number of recombinant bacteria surviving in various organs 2 weeks after immunization. Our data suggest that the immunogenicity of attenuated Salmonella vaccine strains does not correlate with either the number of persisting bacteria after immunization or the levels of in vitro expression of the antigen carried. Rather, the PhoPc phenotype appears to provide the unique ability inSalmonella to induce immune responses against HPV16 VLPs.

Chimeric Hepatitis B Core Antigen Particles Containing B- and Th-Epitopes of Human Papillomavirus Type 16 E7 Protein Induce Specific Antibody and T-Helper Responses in Immunised Mice

Virology ◽  
1994 ◽  
Vol 200 (2) ◽  
pp. 547-557 ◽  
Author(s):  
Robert W. Tindle ◽  
Karen Herd ◽  
Patricia Londoño ◽  
Germain J.P. Fernando ◽  
Steven N. Chatfield ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hepatitis B ◽  
Specific Antibody ◽  
Core Antigen ◽  
T Helper ◽  
Human Papillomavirus Type 16 ◽  
Hepatitis B Core Antigen

scholarly journals Virus-like particles displaying conserved toxin epitopes stimulate broadly reactive, polyspecific, murine antibody responses capable of snake venom recognition

2021 ◽  
Author(s):  
Stefanie K. Menzies ◽  
Charlotte A. Dawson ◽  
Edouard Crittenden ◽  
Rebecca Edge ◽  
Steven R. Hall ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Antibody Responses ◽  
Core Antigen ◽  
Important Species ◽  
Virus Like Particles ◽  
Venom Toxins ◽  
Group I ◽  
First Choice ◽  
Antibody Titres ◽  
Hepatitis B Core Antigen

Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like particles can stimulate a robust and focused antibody response capable of recognising venom toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding to predicted conserved regions of group I phospholipase A2 and three finger toxins, were engineered for display on the surface of hepatitis B core antigen virus like particles and used to immunise female CD1 mice over a 14-weeks. Antibody responses to all venom epitope virus like particles were detectable by ELISA by the end of the immunisation period, although total antibody and epitope specific antibody titres were variable against the different epitope immunogens. Immunoblots using pooled sera demonstrated recognition of various venom components in a diverse panel of six elapid venoms, representing three continents and four genera. Finally, pooled terminal sera was compared to conventional antivenom via quantitative immunoblot, and demonstrated superior recognition of lower-molecular weight elapid venom toxins. This study demonstrates proof-of-principle that virus like particles engineered to display conserved toxin linear epitopes can elicit specific antibody responses in mice which are able to recognise a geographically broad range of elapid venoms.

scholarly journals Characterization of a Major Neutralizing Epitope on Human Papillomavirus Type 16 L1

1999 ◽  
Vol 73 (6) ◽  
pp. 4882-4889 ◽  
Author(s):  
Wendy I. White ◽  
Susan D. Wilson ◽  
Frances J. Palmer-Hill ◽  
Robert M. Woods ◽  
Shin-je Ghim ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Site Directed Mutagenesis ◽  
Binding Studies ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Complete Restoration ◽  
Viral Stock

ABSTRACT Persistent infection with human papillomavirus type 16 (HPV-16) is strongly associated with the development of cervical cancer. Neutralizing epitopes present on the major coat protein, L1, have not been well characterized, although three neutralizing monoclonal antibodies (MAbs) had been identified by using HPV-16 pseudovirions (R. B. Roden et al., J. Virol. 71:6247–6252, 1997). Here, two of these MAbs (H16.V5 and H16.E70) were demonstrated to neutralize authentic HPV-16 in vitro, while the third (H16.U4) did not. Binding studies were conducted with the three MAbs and virus-like particles (VLPs) composed of the reference L1 sequence (114K) and three variant L1 sequences: Rochester-1k (derived from viral stock DNA), GU-1 (derived from cervical biopsy DNA), and GU-2 (derived from biopsy DNA, but containing some sequence changes likely to be artifactual). While all three MAbs bound to 114K and Rochester-1k VLPs, GU-1 VLPs were not recognized by H16.E70, and both H16.E70 and H16.V5 failed to bind to GU-2 VLPs. Site-directed mutagenesis was used to replace disparate amino acids in the GU-2 L1 with those found in the 114K L1. Alteration of the amino acid at position 50, from L to F, completely restored H16.V5 binding and partially restored H16.E70 binding, while complete restoration of H16.E70 binding occurred with GU-2 VLPs containing both L50F and T266A alterations. Immunization of mice with L1 variant VLPs revealed that GU-2 VLPs were poorly immunogenic. The L50F mutant of GU-2 L1, in which the H16.V5 epitope was restored, elicited HPV-16 antibody responses comparable to those obtained with 114K VLPs. These results demonstrate the importance of the H16.V5 epitope in the generation of potent HPV-16 neutralizing antibody responses.

Immunisation of mice using Salmonella typhimurium expressing human papillomavirus type 16 E7 epitopes inserted into hepatitis B virus core antigen

Vaccine ◽  
1996 ◽  
Vol 14 (6) ◽  
pp. 545-552 ◽  
Author(s):  
L. Patricia Londoño ◽  
Steven Chatfield ◽  
Robert W. Tindle ◽  
Karen Herd ◽  
Xiao-Ming Gao ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Salmonella Typhimurium ◽  
Core Antigen ◽  
Human Papillomavirus Type 16 ◽  
Virus Core ◽  
B Virus

scholarly journals Transcriptional Activation of the Telomerase hTERT Gene by Human Papillomavirus Type 16 E6 Oncoprotein

2001 ◽  
Vol 75 (9) ◽  
pp. 4467-4472 ◽  
Author(s):  
Tim Veldman ◽  
Izumi Horikawa ◽  
J. Carl Barrett ◽  
Richard Schlegel
Keyword(s):  
Human Papillomavirus ◽  
Transcriptional Activation ◽  
Transcriptional Control ◽  
Regulatory Region ◽  
Rnase Protection ◽  
Hpv 16 ◽  
Htert Gene ◽  
Human Papillomavirus Type 16 ◽  
E6 Gene

ABSTRACT The E6 and E7 oncogenes of human papillomavirus type 16 (HPV-16) are sufficient for the immortalization of human genital keratinocytes in vitro. The products of these viral genes associate with p53 and pRb tumor suppressor proteins, respectively, and interfere with their normal growth-regulatory functions. The HPV-16 E6 protein has also been shown to increase the telomerase enzyme activity in primary epithelial cells by an unknown mechanism. We report here that a study using reverse transcription-PCR and RNase protection assays in transduced primary human foreskin keratinocytes (HFKs) shows that the E6 gene (but not the E7 gene) increases telomerase hTERT gene transcription coordinately with E6-induced telomerase activity. In these same cells, the E6 gene induces a 6.5-fold increase in the activity of a 1,165-bp 5′ promoter/regulatory region of the hTERT gene, and this induction is attributable to a minimal 251-bp sequence (−211 to +40). Furthermore, there is a 35-bp region (+5 to +40) within this minimal E6-responsive promoter that is responsible for 60% of E6 activity. Although the minimal hTERT promoter contains Myc-responsive E-box elements and recent studies have suggested a role for Myc protein in hTERT transcriptional control, we found no alterations in the abundance of either c-Myc or c-Mad in E6-transduced HFKs, suggesting that there are other or additional transcription factors critical for regulating hTERT expression.

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