The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Department of Health

Johns Hopkins University

New England Medical Center Hospitals. Inc.

Deutsches Krebsforschungszentrum, the German Cancer Research Center

John T. Schiller

Douglas R. Lowy

Heather Greenstone

Douglas R Lowy

John T Schiller

Reinhard Kirnbauer

Bryce Chackerian

Richard B S Roden

Diana V Pastrana

Jeff Roberts

Ratish Gambhira

Jeffrey Roberts

Elliot J Androphy

Richard B Roden

Disclosed herein are methods of detecting tumors, monitoring cancer therapy, and selectively inhibiting the proliferation and/or killing of cancer cells utilizing a papilloma pseudovirus or a papilloma virus-like particle (VLP).

Papillomavirus pseudoviruses for detection and therapy of tumors

The invention comprises a method for inducing broadly cross-neutralizing antibodies against cutaneous and mucosal papillomavirus types or against heterologous papillomavirus types in humans comprising administering to a human in need thereof an immunogenic peptide or protein (or polynucleotide encoding therefor), where the immunogenic peptide or protein is: (a) a peptide or protein of at least 10 amino acid residues in length having a sequence corresponding to either a sequence from the N terminal amino acids 1-200 of papillomavirus L2 protein (for cross-neutralizing antibodies against cutaneous and mucosal papillomavirus types) or a sequence from the N terminal amino acids 1-88 of papillomavirus L2 protein (for cross-neutralizing antibodies against heterologous papillomavirus types), (b) a peptide or protein of at least 10 amino acid residues in length with at least 55% identity with the sequence from (a), or (c) a peptide or protein as defined in either (a) or (b) which is conjugated or fused to a protein or peptide other than a papillomavirus L2 protein or peptide.

Papillomavirus L2 N-terminal peptides for the induction of broadly cross-neutralizing antibodies

The invention described herein relates to compositions and methods for stimulating immune responses in vivo against a tolerogen. Novel biotechnological tools, pharmaceuticals, therapeutics and prophylactics, which concern chimeric or conjugated virus-like particles, and methods of use of the foregoing are provided for the study of B cell tolerance and the treatment or prevention of human diseases, which involve the onset of B cell tolerance, such as chronic viral infection, chronic inflammatory disease, and neoplasia.

Virus-like particles for the induction of autoantibodies

The present invention provides a papillomavirus-like particle, characterized as having conformational epitopes, comprising a papillomavirus L1 product and a papillomavirus L2 fusion product; and related synthetic DNA molecules, host cells, methods and vaccines.

Chimeric papillomavirus-like particles

Mouse titers after two immunizations with VLPs alone

Recombinant papillomavirus capsid proteins that are capable of self assembly into capsomer structures and viral capsids that comprise conformational antigenic epitopes are provided. The capsomer structures and viral capsids, consisting of the capsid proteins that are expression products of a bovine, monkey or human papillomavirus L1 conformational coding sequence proteins, can be prepared as vaccines to induce a high titer neutralizing antibody response in vertebrate animals. The self assembling capsid proteins can also be used as elements of diagnostic immunoassay procedures for papillomavirus infection.

Self-assembling recombinant papillomavirus capsid proteins

The invention provides an infectious papillomavirus pseudoviral particle useful in gene transfer comprising: (a) a papillomavirus vector DNA which comprises an E2 binding site and an expression cassette comprising a gene and a sequence controlling expression of said gene; and (b) a papillomavirus capsid which comprises L1 and L2 structural proteins, such that said capsid encapsidates said vector DNA, wherein said gene is derived from a first biological species and said L1 structural protein is derived from a second biological species and said first biological species is different from said second biological species.

Infectious papillomavirus pseudoviral particles

Growing community of inventors

Bethesda, MD, United States of America

Douglas R Lowy