Current invention describes the methods to prepare vaccines, and to use such vaccines in the vaccination and treatment of human disease, e.g., the human immunodeficiency virus (HIV) infections and cancer. More specifically, the present invention provides a vaccine and method for making same which is effective to elicit a desired antibody against a target antigen comprising a primary immunogen and a secondary immunogen, wherein the primary immunogen is effective to elicit B cell receptors (BCRs) that are on the maturational pathway of the desired antibody and have an intermediate degree of somatic mutational diversity, and the secondary immunogen comprises an epitope of the desired target antibody and is effective to further diversify the BCRs sufficient to form mature BCRs having the identical or substantially identical sequence as the desired antibody.

Applications: 
Treatment and prevention of HIV infection

Advantages: 

• Novel methods to design vaccines for HIV treatment and prevention
• May also be used for designing vaccines for cancer treatment

Development Status: 
In vitro data available

Market: 
HIV therapeutics and preventatives

Publications:

1. MY Zhang, Y Shu, S Phogat, X Xiao, F Cham, P Bouma, A Choudhary, YR Feng, I Sanz, S Rybak, CC Broder, GV Quinnan, T Evans, DS Dimitrov. Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library. J Immunol Methods. 2003 Dec;283(1-2):17-25.  [PubMed abs]
2. MY Zhang, X Xiao, IA Sidorov, V Choudhry, F Cham, PF Zhang, P Bouma, M Zwick, A Choudhary, DC Montefiori, CC Broder, DR Burton, GV Quinnan Jr, DS Dimitrov. Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J Virol. 2004 Sep;78(17):9233-9242.  [PubMed abs]
3. Z Zhu, AS Dimitrov, KN Bossart, G Crameri, KA Bishop, V Choudhry, BA Mungall, YR Feng, A Choudhary, MY Zhang, Y Feng, LF Wang, X Xiao, BT Eaton, CC Broder, DS Dimitrov. Potent neutralization of Hendra and Nipah viruses by human monoclonal antibodies. J Virol. 2006 Jan;80(2):891-899.  [PubMed abs]
4. MY Zhang, V Choudhry, IA Sidorov, V Tenev, BK Vu, A Choudhary, H Lu, GM Stiegler, HW Katinger, S Jiang, CC Broder, DS Dimitrov. Selection of a novel gp41-specific HIV-l neutralizing human antibody by competitive antigen panning. J Immunol Methods. 2006 Dec 20;317(1-2):21-30.  [PubMed abs]
5. V Choudhry, MY Zhang, IA Sidorov, JM Louis, I Harris, AS Dimitrov, P Bouma, F Cham, A Choudhary, SM Rybak, T Fouts, DA Montefiori, CC Broder, GV Quinnan Jr, DS Dimitrov. Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gpI40) isolated from a patient (R2) with broadly HIV-l neutralizing antibodies. Virology. 2007 Jun 20;363(1):79-90.  [PubMed abs]
6. Z Zhu, S Chakraborti, Y He, A Roberts, T Sheahan, X Xiao, LE Hensley, P Prabakaran, B Rockx, IA Sidorov, D Corti, L Vogel, Y Feng, JO Kim, LF Wang, R Baric, A Lanzavecchia, KM Curtis, GJ Nabel, K Subbarao, S Jiang, DS Dimitrov. Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies. Proc Natl Acad Sci USA. 2007 Jul 17;104(29):12123-12128.  [PubMed abs]
7. Z Zhu, KN Bossart, KA Bishop, G Crameri, AS Dimitrov, JA McEachern, Y Feng, D Middleton, LF Wang, CC Broder, DS Dimitrov. Exceptionally potent cross-reactive neutralization of Nipah and Hendra viruses by a human monoclonal antibody. J Infect Dis. 2008 Mar 15;197(6):846-853.  [PubMed abs]
8. MY Zhang, BK Vu, A Choudhary, H Lu, M Humbert, H Ong, M Alam, RM Ruprecht, G Quinnan, S Jiang, DC Montefiori, JR Mascola, CC Broder, BF Haynes, DS Dimitrov. Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody which recognizes a novel conformational epitope on gp41 and lacks reactivity against self antigens. J Virol. 2008 Jul;82(14):6869-6879.  [PubMed abs]

U.S. Provisional Application No. 61/104,706 filed 11 Oct 2008 (HHS Reference No. E-322-2008/0-US-01)

Inventor: 
Dimiter S. Dimitrov (NCI)

Licensees Sought: 
Available for licensing.

Collaborative Research Opportunity: 

The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this method.  Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.