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Monday, 04/05/2010 6:30:53 PM

Monday, April 05, 2010 6:30:53 PM

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4-5-10: DukeHealth announces 1st Duke/PPHM HIV Collab. article in JEM

The first Duke/PPHM HIV Collab. (Haynes/Moody/Thorpe/PPHM/Affitech, CHAVI-NIH/CAVD-Gates) article has been published online in the “Journal of Experimental Medicine” (JEM), per a 4-5-10 Duke Medicine News article titled, “Scientists Identify How a Novel Class of Antibodies Inhibits HIV Infection”.

Remember, this is Duke’s announcement of & commentary by Drs. Haynes & Moody about a new JEM Haynes/Moody/Thorpe/S.King/P.Chen/etal Anti-Lipids/HIV article, which I believe parallels the Moody/Haynes/Thorpe/PPHM/Affitech Anti-Lipids (PGN632 etal) presentation given at AIDS-VACCINE’08 in CapeTown on 10-14-08 (see details below). The JEM article itself is accessible (via subscription; public can see Abstract) at http://jem.rupress.org – click on NEWEST-ARTICLES. JEM posted the article on April 5th, and it will ultimately roll over into the April 12, 2010 print issue of JEM (similar AOP-process as Nature Medicine)…

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4-5-10 DUKE: “Scientists Identify How a Novel Class of Antibodies Inhibits HIV Infection”
By Duke Medicine News ( http://www.dukehealth.org/health_library/news )
Pub. Apr. 5, 2010
http://www.dukehealth.org/health_library/news/scientists_identify_how_a_novel_class_of_antibodies_inhibits_hiv_infection

Scientists at Duke University Medical Center have identified a set of naturally occurring antibodies that can block one of the key ways the AIDS virus gains entry into certain blood cells. They say the discovery, published online in The Journal of Experimental Medicine [ http://jem.rupress.org ], expands traditional notions about how the immune system fights HIV and offers a potential new strategy for HIV vaccine design.

Researchers have been puzzled and frustrated for years by antibody responses to HIV. In most infections, antibodies that fight off invading pathogens show up quickly and get right to work. But with HIV, the most powerful antibodies typically don’t materialize until weeks or even months after initial infection -- way too late to be effective.

“The beauty of this newly identified set of antibodies -- called polyreactive anti-phospholipid antibodies -- is that they are so potent against the type of virus that establishes infection during mucosal transmission,” says Anthony Moody, MD, a member of the Center for HIV/AIDS Vaccine Immunology (CHAVI) at Duke and lead author of the study appearing in The Journal of Experimental Medicine.

“Our research suggests we may be able to harness them and enhance their anti-viral activity with a vaccine to fight HIV directly,” Moody says.

Moody says the antibodies, PGN632, P1, IS4 and CL1, do not appear to have any pathogenic features, even though other members of the class do. Earlier studies by others have demonstrated that anti-phospholipid antibodies have anti-viral effects, but “what we have done in this paper is to show how they do that,” Moody says. Through a series of laboratory tests on blood taken from HIV-infected patients as well as healthy volunteers, Moody discovered that when these antibodies bind to white blood cells (monocytes), it causes them to secrete substances called chemokines that block HIV from docking with its favorite entry point into a blood cell, the CCR5 receptor.

“In other words, they don’t go after individual viral particles directly, but instead, indirectly, by creating a chemical roadblock at one of the virus’ most commonly used portals.”

That doesn’t happen all the time, however. The study showed antiviral activity in only 85% of the blood they tested -- and only in the presence of monocytes. Investigators believe the finding has particular strategic importance because most of the HIV strains use the CCR5 receptor to gain entry into a cell. Since it is one of the earliest events in the process of infection, being able to potentially intervene at that juncture could be meaningful.

While the findings still have to be tested clinically, they do suggest a new way the immune system might be manipulated to thwart HIV, said Barton Haynes, MD, director of CHAVI and the Duke Human Vaccine Institute and senior author of the study. “There are two parts of the immune system -- the innate and adaptive components -- and this study shows a vaccine that could elicit these polyreactive antibodies could recruit both components to fight HIV.” “We have long assumed that a successful vaccine would probably need to attack HIV on multiple fronts," Haynes says. “These findings have given us one more potential way to use the immune system to fight HIV.”

The study was supported by a Collaboration for AIDS Vaccine Discovery [CAVD] grant from the Bill and Melinda Gates Foundation, a Veterans Affairs Merit Review Award, an NIAID NIH grant, the Center for HIV/AIDS Vaccine Immunology [CHAVI] as well as resources from the University of Alabama and the Birmingham Center for AIDS Research.

Colleagues from Duke who contributed to the study include David Montefiori, Hua-Xin Liao, S. Munir Alam, Richard Seacre, M. Kelly Plonk, Daniel Koznik, Mark Drinker, Shi-Mao Xia, Laura Sutherland, Georgia Tomaras, Thomas Denny, and Kwan-Ki Hwang.

Others who contributed include Ian Giles, University College, London; John Kappes, Christina Ochsenbauer-Jambor, and Tara Edmonds, University of Alabama; Melina Soares, Gustavo Barbero, and Philip Thorpe [PPHM SAB], University of Texas Southwestern Medical Center; Donald Forthal and Gary Landucci, University of California-Irvine; Connie Chang and Steven King, Peregrine Pharmaceuticals; and Pojen Chen, University of California-Los Angeles.
*end*

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4-5-10, Journal of Experimental Medicine (JEM) Online
Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce B-Chemokines
Submitted: 6-11-09, Accepted: 2-23-10, Pub-online: 4-5-10
(To be included in the 4-12-10 JEM print issue) http://jem.rupress.org
ABSTRACT:
Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that 4 human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to ~10 ug/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1A and MIP-1B. The release of these B-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.
http://jem.rupress.org/content/early/2010/04/02/jem.20091281.abstract
AUTHORS:
M. Anthony Moody 1,2, Hua-Xin Liao 1,3, S. Munir Alam 1,3,4, Richard M. Scearce 1, M. Kelly Plonk 1, Daniel M. Kozink 1, Mark S. Drinker 1, Ruijun Zhang 1, Shi-Mao Xia 1, Laura L. Sutherland 1, Georgia D. Tomaras 1,5,6, Ian P. Giles 7, John C. Kappes 8,9,10, Christina Ochsenbauer-Jambor 8, Tara G. Edmonds 9, Melina Soares 11, Gustavo Barbero 11, Donald N. Forthal 12, Gary Landucci 12, Connie Chang 13, Steven W. King 13, Anita Kavlie 14, Thomas N. Denny 1, Kwan-Ki Hwang 1, Pojen P. Chen 15, Philip E. Thorpe 11, David C. Montefiori 5, Barton F. Haynes 1,3,6
- - - - - - - - -
• 1-6: Duke Univ. Medical Center, Durham, NC: 1=Duke Human Vaccine Institute and 2=Dept. of Pediatrics, 3=Dept. of Medicine, 4=Dept. of Pathology 5=Dept. of Surgery, 6=Dept. of Immunology
• 7=Centre for Rheumatology Research, Univ. College London Div. of Medicine and Medical Molecular Biology Unit, Inst. of Child Health, Univ. College, London UK
• 8-9: Univ. of Alabama/Birmingham: 8=Dept. of Medicine, 9=Dept. of Pathology
• 10=Veterans Affairs Medical Center Res. Service, Birmingham, AL
• 11=Dept. of Pharmacology, Univ. of Texas SW Medical Center, Dallas, TX
• 12=Division of Infectious Diseases, Dept. of Medicine, Univ. of California Irvine School of Medicine, Irvine, CA
• 13=Peregrine Pharmaceuticals, Inc., Tustin, CA
• 14=Affitech AS, Oslo, Norway
• 15=Dept. of Medicine, Univ. of California, Los Angeles, CA
- - - - - - - - -
ABOUT JEM ( http://jem.rupress.org ): “Since its inception in 1896, The Journal of Experimental Medicine (JEM) has published papers on the physiological, pathological, and molecular mechanisms that encompass the host response to disease. The journal prioritizes studies on intact organisms and has made a commitment to publishing studies on human subjects.”

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PPHM PR 4-5-10: ”Peregrine Pharmaceuticals Reports Data from Newly Published Research Reinforcing Potential of Targeting PS in HIV Infection
• Article in Journal of Experimental Medicine Shows that PS-Targeting Antibodies Can Block One of the Ways the AIDS Virus Gains Entry into Blood Cells”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=456463
TUSTIN, April 5, 2010: Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) today announced the publication of data showing phosphatidylserine (PS)-targeting antibodies can block one of the key ways the AIDS virus gains entry into certain blood cells. The data were generated by scientists at Duke University as part of their ongoing AIDS vaccine research. The article titled "Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce B-Chemokines" is available online today and will be published in the April 12, 2010 edition of the Journal of Experimental Medicine [ JEM: http://jem.rupress.org ]. Peregrine's PS-targeting antibodies are currently in clinical development for the treatment of cancer and HCV infections.

In early stage in vitro studies reported by Dr. Anthony Moody of Duke University, lead author of the publication, PS-targeting antibodies developed or licensed by Peregrine blocked HIV from docking with its most commonly used entry point into blood cells--the CCR5 receptor. The antibodies accomplished this indirectly, by binding to white blood cells called monocytes and causing them to secrete proteins called chemokines, which have the ability to block entry of HIV into the cell. In the presence of monocytes, the antibodies prevented HIV infection in vitro 85% of the time in these studies. Investigators believe the finding has particular strategic importance because most HIV strains use the CCR5 receptor to gain entry into a cell. In addition, it is one of the earliest events in the process of infection, so being able to intervene at this juncture could potentially be clinically useful.

Dr. Philip Thorpe, professor of pharmacology at UT Southwestern Medical Center, a pioneer in the development of PS-targeting therapies and an author of the new publication commented, "This study from our colleagues at Duke University illuminates another intriguing aspect of phospholipid-targeting antibodies--the diversity of their anti-viral mechanisms and broad spectrum anti-viral potential. The PS-targeting antibodies in this study showed potent ability to induce specific effects that impact viruses, in this case by stimulating the production of immune-related proteins that block the entry of HIV into cells. We look forward to the results of additional studies of these antibodies that are planned at Duke."

Barton Haynes, M.D., director of the Duke Human Vaccine Institute and senior author of the study commented, "These results indicate that targeting a host cell lipid such as PS as an anti-viral strategy is a promising concept of relevance to new therapeutic and possibly prophylactic innovations for HIV."

Peregrine's most advanced PS-targeting antibody bavituximab is currently being studied in a clinical trial for the treatment of patients co-infected with hepatitis C virus (HCV) and HIV. Earlier Phase I studies in HCV patients showed that bavituximab was well tolerated and it exhibited encouraging signs of anti-viral activity. Under a major biodefense initiative, bavituximab and a fully human equivalent antibody are also in preclinical development for the treatment of viral hemorrhagic fevers (VHF). In November, 2009 Peregrine researchers presented positive data on progress in this program, showing that the PS-targeting antibodies increase survival in a model of lethal VHF infection [ 11-18-09, DTRA/TMTI Conf. http://tinyurl.com/ycrrwub ].

"This publication is the latest in a series of presentations and publications that supports the potential of PS as a target in HIV infection and provides new insights into the unique mechanisms of action of our PS-targeting antibodies," said Steven W. King, president and CEO of Peregrine. "While past studies have focused on the broad nature of the PS target, these new data reveal that some of these antibodies may also have highly specific effects."

Anti-Phospholipid Human Monoclonal Antibodies Inhibit CCR5-Tropic HIV-1 and Induce B-Chemokines, M. Anthony Moody et al.
Journal of Experimental Medicine. Published Online First April 5, 2010.
[ http://jem.rupress.org ]

The study was supported by a Collaboration for AIDS Vaccine Discovery [CAVD] grant from the Bill and Melinda Gates Foundation, a Veterans Affairs Merit Review Award, an NIAID NIH grant, the Center for HIV/AIDS Vaccine Immunology [CHAVI] as well as resources from the University of Alabama and the Birmingham Center for AIDS Research.

ABOUT PS-TARGETING ANTI-VIRAL AGENTS
Phosphatidylserine (PS), a lipid molecule normally found only on the inside of cell membranes, becomes exposed on the outside of the membranes of viruses and virally infected cells. A growing body of published scientific research confirms that exposed PS is involved in the pathogenesis of many serious infectious diseases. Exposed PS enables viruses to evade immune recognition and dampens the body's normal responses to infection. By masking the exposed PS, PS-targeting antibodies are believed to block these effects, allowing the body to develop a robust immune response to the pathogen.

Peregrine's PS-targeting antibodies have been shown to help clear infectious virus from the bloodstream and to induce antibody-dependent cellular cytotoxicity. PS is exposed on the outer membrane of cells infected with a wide range of viruses, including HIV, influenza, herpes simplex viruses, hemorrhagic fever viruses, cytomegalovirus, measles and members of the smallpox and rabies virus families. Because the PS target is host-derived rather than pathogen-derived, PS-targeting antibodies are expected to be less susceptible to the viral genomic mutations that lead to anti-viral drug resistance. Peregrine is the exclusive licensee of broad patents covering anti-viral applications of PS-targeting antibodies issued to the University of Texas System.

ABOUT PEREGRINE PHARMACEUTICALS
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing three separate clinical programs in cancer and HCV infection with its lead product candidates bavituximab and Cotara®. Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at http://www.peregrineinc.com .
Safe Harbor *snip*
Contacts: GendeLLindheim BioCom Partners
Investors: 800-987-8256, info@peregrineinc.com
Media: Barbara Lindheim, 212-918-4650

= = = = = = = = = = = = = = = = = = = = = Followup Articles (more to follow):

4-5-10 MSN: “Research on Antibodies May Aid Vaccine Development”
By Randy Doting, HealthDay Reporter
http://health.msn.com/health-topics/aids-hiv/articlepage.aspx?cp-documentid=100256597
MONDAY, April 5 (HealthDay News): Researchers report that they've gained more insight into how the body fights off HIV, a finding that offers a possible new avenue toward a vaccine against the virus, which causes AIDS. At the moment, there's no way to know whether the research will help scientists develop a vaccine. HIV remains an extremely stubborn enemy. Still, the findings do give scientists an idea of how to prepare the body to meet the threat of HIV, "a possible way that one could think about the kinds of response you'd want to have on hand before a virus shows up," said study author Dr. M. Anthony Moody, chief medical officer at Duke University's Human Vaccine Institute. The findings are reported online April 5 2010 in the Journal of Experimental Medicine.
The study examines antibodies, the foot soldiers of the immune system that gather to fight off invaders. The researchers found four kinds of antibodies that appear to create a barrier that prevents HIV from getting into a kind of door in cells. That door, known as a receptor, is an entry point for HIV in the vast majority of cases. The 4 antibodies work differently than their counterparts because they focus on creating a barricade to protect the cells instead of doing direct battle with the virus cells, Moody said.
It's not clear if having more of these antibodies would help people do a better job of fighting off HIV. There's definite room for improvement in that area, Moody said. "One of the fundamental problems that research in HIV has faced is that when people become infected, they don't typically mount an antibody response that's very effective at controlling a response early on," Moody said. "The response to the virus is much slower, and it's delayed and comes in stages. The kinds of antibodies that are produced do appear to have an effect, but the virus always seems to stay one step ahead." By contrast, the body has a more effective antibody response to viruses such as influenza, he said.
The next step is to "understand even more deeply what's going on," Moody said. Another step would be to consider whether to test the antibodies in animals and people to see whether they boost their immune systems, he said.
Rowena Johnston, VP Research with amfAR, the Foundation for AIDS Research in New York City, said the research reflects a feeling in the HIV vaccine research field that "what they need to do is go back to the drawing board." The challenge, she said, is that many steps would be involved in getting the antibodies to protect cells against HIV. "The more steps you introduce into it, the more things that can go wrong," she said. The research does provide more information about how the process works, she said, "but it doesn't mean the next step is voila, we have a vaccine."
*end*
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= = = = = = = = = = = = = = BACKGROUND:
10-14-08, MOODY/HAYNES, AIDS-VACCINE'08/CAPETOWN:
Oct. 14, 2008, Oral Abstracts 03: “Neutralizing Antibodies & Immune Escape”
#OA03-06 ”Anti-lipid Human Monoclonal Antibodies Inhibit HIV-1 Infection of PBMC by Binding to Host Cells”
TONY MOODY [Dir., Laboratory of B cell Immunology, Duke Univ. MC]
MA Moody 1, MK Plonk 1, L Fuller 1, H Liao 1, S Xia 1, MS Drinker 1, TC Gurley 1, RM Scearce 1, GD Tomaras 1, C Chang 2, S King 2, A Kavlie 3, PE Thorpe 4, SM Alam 1, PP Chen 5, DC Montefiori 6, BF Haynes 1
1 Duke University Medical Center, Durham, NC
2 Peregrine Pharmaceuticals, Tustin, CA
3 Affitech AS, Oslo, N-0349, Norway
4 University of Texas Southwestern Medical Center, Dallas, TX
5 UCLA School of Medicine, Los Angeles, CA
6 Dept. of Surgery, Duke University Medical Center, Durham, NC
BACKGROUND:
HIV-1-infected or vaccinated humans rarely make broadly-reactive neutralizing antibodies. Some antibodies against conserved Env epitopes share similarities with autoantibodies; one hypothesis is such antibodies are downregulated by immune tolerance. The observation that AIDS may be rare in primary autoimmune disease patients (1) prompted the hypothesis that autoimmune disease patients with defective tolerance mechanisms may make antibodies that in some manner protect against HIV-1 infection. Methods: We studied a panel of human anti-lipid mAbs from autoimmune disease patients and healthy controls. Mabs IS4, CL1, P1, and PGN632 bind cardiolipin and phosphatidylserine independent of b2-glycoprotein I; mAbs B1, B2, PGN634, and PGN635 require b2-glycoprotein I for lipid binding. Inhibition of HIV-1 infection was studied using HIV-1 Env pseudoviruses in TZM/bl cells and using whole virus assays in peripheral blood mononuclear cells (PBMC). MAb interaction with Env, lipids, and cells was determined by surface plasmon resonance (SPR), flow cytometry, and fluorescent microscopy.
RESULTS:
No mAbs bound HIV-1 wild-type Envs by SPR and none significantly neutralized HIV-1 primary isolate pseudoviruses in the TZM/bl assay. In PBMC, b2-glycoprotein I-dependent mAbs minimally inhibited infection. In contrast, b2-glycoprotein I-independent anti-lipid mAbs (PGN632, P1, IS4, CL1) inhibited HIV-1 primary isolate infection of PBMC (IC80s<0.02 to 45 mg/ mL). The most potent mAb PGN632 inhibited 7/7 B & C clade HIV-1 isolates (IC80s<0.02-0.16 mg/mL) and SHIV-SP162P3 (IC80 0.06 mg/mL). Cell preincubation and virus capture studies showed the mAbs acted at host cell surfaces to inhibit HIV-1 infection. Immunofluorescence of CD4b T cells showed the mAbs bound to lipid rafts.
CONCLUSION:
Anti-lipid human mAbs inhibit HIV-1 infection in vitro in PBMC likely by binding CD4þ T cell lipid rafts. Testing these mAbs in passive therapy trials in vivo in non-human primates will be important to determine their protective effect. Nonpathogenic anti-lipid antibodies may provide a target for HIV-1 vaccine development.
PAGE 57, #OA03-06: HivVaccineEnterprise.org link: http://tinyurl.com/7dnmpe

1-6-09, NIAID REVIEW OF MOODY/HAYNES’ 10-14-08 PAPER AT AIDS’08/CAPETOWN:
“NEUTRALIZING ANTIBODIES TO THWART HIV”
…Tony Moody of Duke Univ. School of Medicine established a panel of b2-glycoprotein I independent anti-lipid monoclonal antibodies from auto-immune disease patients. These antibodies failed to neutralize HIV in the standardized TZM-bl reporter cell line assay. However, they neutralized virus in the PBMC assay, apparently through release of b-chemokines (MIP1a, MIP1b) by monocytes in the culture. Such chemokines interfere with virus entry through the CCR5 receptor. Furthermore, neutralization could be reverted by antibodies against MIP1a and MIP1b. These anti-lipid antibodies stick to the host target cell and not the virus to prevent infection. A vaccine that induces such antibodies may not be able to directly neutralize HIV but it may reduce virus spreading…
http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm

3-17-09. CAVD 2006-2008 RECAP REPORT – (57-PG PDF):
...“researchers in the Haynes VDC have discovered that anti-lipid antibodies in fact may play a role in HIV-1 protection. They found that anti-lipid antibodies produced in autoimmune disease have the capacity to broadly inhibit the infection of peripheral blood mononuclear cells by virtually all CCR5-dependent HIV-1 primary isolates. They are working now to translate this finding into a novel strategy of HIV-1 vaccine development.” http://tinyurl.com/d2jpm9

5-1-09, DR. BARTON HAYNES, CHAVI UPDATE:
“The (CHAVI) B Cell Discovery Team has defined a class of anti-lipid antibodies with breadth of protection in vitro PBMC assay for R5 transmitted/founder strains. (Nature Medicine, submitted 2009)”. http://tinyurl.com/d2ucmw

7-14-09 QTLY. CONF. CALL: http://tinyurl.com/nt4zql
SK: “We have been working with them for quite some time. The initial pub. has been submitted and is in the process of being reviewed. You may have comments and what have you - so it’s in the progress of being published. Our focus has really moved beyond that research, obviously because that’s already been done, and we are still very active with the group at Duke. In fact, we’re expanding our collaboration with them, looking at many different areas, a number of different antibodies, so the collaboration is alive and well, and still very active with them, so this first publication is only the beginning of what we expect to be a really fruitful long-term relationship.”

9-3-09 QTLY. CONF. CALL: http://tinyurl.com/nuykr2
SK: “Certainly, our goal is to see a number of publications, presentations, and such coming from this research to let the public know how the pgms are proceeding and what the results are looking like as they move forward, and also to shine a light on what our future plans are for the pgm. I think we’ll have opportunities to, not just talk about or publish the work we’re doing with our collaborators at Duke and the other institutions involved in researching our anti-viral apps of our PS-technology, but also even some opportunities to present data from the DTRA contract work, and shine some light on how those studies are proceeding. I believe that all of our collaborators are equally interested in seeing that information get out there in really the right format and in the right setting. All those preparations are in the works and I think you’ll see more coming out of the pgms from a public standpoint over the coming months. Clearly we’re excited to get that information out there, because we’re very happy with the way actually all of these studies are progressing and what we’re seeing in the pre-clinical studies.”

12-18-09, DR. HAYNES CHAVI UPDATE (NOV’09): http://tinyurl.com/ykbl2vs
…”We’ve worked with Peregrine for mab production of 11.31(PGN632), 11.17(new?), 1N11(PGN635 FH-Bavi), and Bavituximab for use in NHP passive immunization trials.”

4-2-10(Current), DR. HAYNES DUKE DHVI/VDC ‘MISSION & GOALS’ WEBPAGE
“…We are using a two armed approach to the problem of induction of antibodies that broadly neutralize HIV. The Kelsoe, Haynes and Thorpe laboratories are developing immunogen formulations that trigger B cells normally tolerant to the desired envelope epitopes and regions… Garnett Kelsoe... Laurent Verkoczy… Haynes…, and Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine (PS) autoantibodies to protection from HIV infection. The team has recently found that non-pathogenic anti-lipid antibodies that do not require beta-2-glycoprotein-1 for lipid binding do prevent HIV-1 & SHIVSF162P3 (and all R5 HIVs tested from infecting PBMC in vitro, and a prototype of non-pathogenic anti-lipid antibodies will be studied in non-human primates in vivo for the ability to protect against R5 SHIV infection.”
http://tinyurl.com/674936

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The War on HIV…
GLOBAL HIV VACCINE ENTERPRISE http://www.hivvaccineenterprise.org
Comprised of 2 “implementation projects”:
1. CHAVI - Center for HIV/AIDS Vaccine Immunology http://www.chavi.org
. . . . . $300mm over 7 years from NIAID to CHAVI (Dir=Bart Haynes, CMO=Tony Moody).
2. CAVD - Collaboration for AIDS Vaccine Discovery http://www.cavd.org
. . . . . $287mm over 5 years from BMGF to CAVD ($15mm to B.Haynes).
. . . . . . .Dr. Haynes’ DHVI/VDC website: http://tinyurl.com/674936

Tony Moody, MD is an Instructor in the Dept. of Pediatrics, Div. of Infectious Diseases at Duke Univ. Medical Center and a faculty member of the Duke Human Vaccine Institute (DHVI). Dr. Moody serves as the CHAVI Chief Medical Officer and oversees the CHAVI B cell Immune Monitoring Core. He is the P.I. of the CHAVI 005 clinical protocol, “Analysis of Host Response to HIV-1 in Autoimmune Disease Patients” and the 008A clinical protocol “Molecular Characterization of HIV-1 Neutralizing Antibody Breadth & Potency in Natural Infection.”
http://humanvaccine.duke.edu/modules/moody/index.php?id=1


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THE DUKE/HAYNES/CAVD/GATES/CHAVI/NIH HIV COLLABORATION:
Duke's B.Haynes DHVI website & CAVD-Reports outline Thorpe’s Role in the CAVD-Gates HIV-Vaccine Initiative:
. . . . . http://tinyurl.com/674936 and http://tinyurl.com/5xwjk4 . . .
…”Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine (PS) autoantibodies to protection from HIV infection.”
…2005-July2009: All Peregrine Public Statements on the Duke HIV Collab: http://tinyurl.com/m4aggy
…10-2008: Short profiles of ~40 Gates/NIH HIV collaborators: http://tinyurl.com/57tanp
4-5-10: DukeHealth announces 1st Duke/PPHM HIV Collab. article in JEM - http://tinyurl.com/yzr2tax
...12-18-09: Dr Haynes CHAVI update (Nov'09): http://tinyurl.com/ykbl2vs
…”We’ve worked with Peregrine for mab production of 11.31(PGN632), 11.17(new?), 1N11(PGN635=FH-Bavi), and Bavituximab for use in NHP passive immunization trials.”
...5-2009: Duke’s Tony Moody is CHAVI’s 'Chief Medical Officer' http://tinyurl.com/m3g9cu
...5-1-09: CHAVI update by Barton Haynes says paper on anti-Lipid antibodies "submitted to Nature Med. 2009" http://tinyurl.com/d2ucmw
…..Haynes: “B Cell Discovery Team has defined a class of anti-lipid antibodies with breadth of protection in vitro PBMC assay for R5 transmitted/founder strains.”
...3-18-09: CFO Paul Lytle on the Duke-HIV Collab. at the Cowen Healthcare Conf: http://tinyurl.com/cal9br
...“We are expecting a high-profile pub., which is currently in process thru Duke Univ., to be presented within the 1st half of 2009.”
...3-17-09 CAVD 2006-2008 Recap Report – (57-pg PDF): http://tinyurl.com/d2jpm9
...“researchers in the Haynes VDC have discovered that anti-lipid antibodies in fact may play a role in HIV-1 protection. They found that anti-lipid antibodies produced in autoimmune disease have the capacity to broadly inhibit the infection of peripheral blood mononuclear cells by virtually all CCR5-dependent HIV-1 primary isolates. They are working now to translate this finding into a novel strategy of HIV-1 vaccine development.”
...10-30-08: CEO S.KING, BIO-INV. Forum (SanFran) - replay w/slides: http://tinyurl.com/664mgd
...SK on Duke/Gates/NIH HIV collab: “At AIDS-VACCINE’08, a key finding was that certain classes of Anti-Phospholipid antibodies broadly neutralize HIV infection. And, in fact, the most potent antibodies were those that were provided by Peregrine. This is a very important finding…”
...10-14-08: “The AIDS Vaccine 2008 Conference”, CapeTown, So.Africa http://tinyurl.com/7dnmpe
......Duke’s B.Haynes & T.Moody present Anti-PS data for 1st time publicly: “The most potent mAb, PGN632 [11.31], inhibited 7/7 B & C clade HIV-1 isolates & SHIV SP162P3... Studies showed the mAbs acted at host cell surfaces to inhibit HIV-1 infection."
…..Dr. Ralph Pantophlet’s summary of T.Moody’s Talk, incl. two PGN632=11.31 test data graphs: http://tinyurl.com/7w4udz.
......SK: "This data opens the door to a # of potential commercial app's incl. post-exposure prophylaxis & topical microbicides” http://tinyurl.com/cxv2st
.....1-24-09: Mojo’s Comparison Graphs of Bavi vs. 11.31(PGN632) against HIV (in-vitro): http://tinyurl.com/dkmrdp
.....1-6-09: NIAID reviews CapeTown AIDS’08, commenting on the Tony Moody Anti-Lipids/PGN632 talk: http://tinyurl.com/7dnmpe
.....1-15-09: JBM’s 'AIDS-Vaccine’08/Capetown Wrapup' (Anti-PS Blog): http://tinyurl.com/8cmmcs
.....2-23-09 Duke article about 2F5, a ‘Rare, Potent Antibody to HIV-1’ – comp. vs. PGN632: http://tinyurl.com/aozpd2
…9-22-08: Haynes CAVD Update: ”The team has recently found that non-pathogenic anti-lipid antibodies that do not require B2GPI for lipid binding do prevent HIV-1 & SHIV-SF162P3 (and all R5 HIVs tested) from infecting PBMC in vitro..." http://tinyurl.com/3g6vbm
…12-2007: UCLA’s Dr. Pojen Chen (active in CHAVI/Duke HIV studies) joins PPHM’s SRB: http://tinyurl.com/2nxcm2
...7-2007: PPHM licenses "certain Anti-PS Antibodies" from UCLA - the Dr. Pojen Chen connection? http://tinyurl.com/5t8jvm
…4-24-07: GATES-FOUND. rep's lecture at U-WASH lists P.Thorpe on CAVD grants map: http://tinyurl.com/3t67gj
...3-2007: Duke’s D.Montefiori Europrise-HIV Assay paper refs. “BAVITUX” & “3G4RHD” http://tinyurl.com/448d8k
…1-27-07: Dr. Haynes report, pg.31: “Labeling of Microparticles by Anti-PS Antibodies”: http://tinyurl.com/289a5g
JBM’s blog on Anti-PS science, esp. HIV: http://anti-ps.blogspot.com
Haynes-BF pubs: http://tinyurl.com/3nspyw , Moody-MA pubs: http://tinyurl.com/5yeh2e
Thorpe-PE pubs: http://tinyurl.com/csjsl
Duke Health News: http://www.dukehealth.org/HealthLibrary/News
CHAVI(NIAID http://www.chavi.org) Progress repts: http://tinyurl.com/ydbwl5k
. . .Newsletters: http://tinyurl.com/y8ug6y9
. . .Reagents, Resources, Datasets: http://tinyurl.com/ylxdpqh
CAVD(BMGF http://www.cavd.org) Progress repts: http://tinyurl.com/47uhtu
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