Merck + Co., Inc.

International Aids Vaccine Initiative

Cornell University

The Scripps Research Institute

Michael P Caulfield

C Richter King

Ruth F Nutt

John S Moore

Andrew J Bett

Christopher Lee Parks

Ian A Wilson

Ivo Lorenz

John W Shiver

Ling Chen

Emilio A Emini

Danilo R Casimiro

Andrew B Ward

Andre Marozsan

Michael Rosenblatt

Simon Hoffenberg

Rogier W Sanders

Albert Cupo

Michael A Chastain

Hansi Dean

P J Klasse

Roberta L McKee

Jean-Philippe Julien

The present application relates to novel HIV-1 envelope glycoproteins, which may be utilized as HIV-1 vaccine immunogens, and antigens for crystallization, electron microscopy and other biophysical, biochemical and immunological studies for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions, which are formulated into the vaccines of the present invention.

HIV-1 envelope glycoprotein

The invention relates to generating a vaccine based on immunogens from viral particles that initially have replication competency but are then inactivated by chemical, biophysical or other methods. The components of this vaccine may be a non-HIV enveloped virus that contains and expresses a gene related to the HIV Envelope gene such that the Envelope protein is expressed on the surface of viral particles. These viral particles may be further treated to reduce their replication competency. The vaccine further may contain components to improve its immunogenicity, tolerability, stability and ease of manufacture.

Viral particles derived from an enveloped virus

An adenoviral vector is described which carries a codon-optimized gag gene, along with a heterologous promoter and transcription terminator. This viral vaccine can effectively prevent HIV infection when administered to humans either alone or as part of a prime and boost regime also with a vaccine plasmid.

Adenovirus carrying gag gene HIV vaccine

The present invention relates to the use of peptide analogues as inhibitors of their respective naturally occurring peptides. The structure of the peptide analogues is exemplified by an internal region of the N-terminus of humoral hypercalcemic factor hHCF, and truncations thereof: hHCF(14-34)NH.sub.2, hHCF(13-34)NH.sub.2, hHCF(12-34)NH.sub.2, hHCF(11-23)NH.sub.2, hHCF(10-34)NH.sub.2, hHCF(9-34)NH.sub.2, hHCF(8-34)NH.sub.2 and various amino acid substitutions.

Humoral hypercalcemic factor antagonists

Growing community of inventors

Lansdale, PA, United States of America

Michael P Caulfield