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cjgaddy

Re: cjgaddy post# 33623

Wednesday, 02/25/2009 10:35:36 AM

Wednesday, February 25, 2009 10:35:36 AM

2-23-09 Duke article about 2F5, a ‘Rare, Potent Antibody to HIV-1’… Recapping what I learned the last couple of days about Barton Haynes’ pursuit of “New & More Broadly HIV-Neutralizing Antibodies”, trigged by the Duke 2F5 article – for linking to iBox.

2-23-09: “Duke Scientists Find Rare, Potent Antibody to HIV-1”
This comment in particular: “the 2F5 antibody is especially valuable because previous research has shown it can successfully neutralize 80% of transmitted HIV viruses.”
http://www.dukehealth.org/HealthLibrary/News/duke_scientists_find_rare_potent_antibody_to_hiv_1

Turns out that mab 2F5 (along with 4E10) may well have been what got Haynes interested in Peregrine’s “Anti-Lipid / Anti-PS” mabs (like PGN632/11.31) in the first place. The Duke news Monday was not about them finding a new broadly neutralizing antibody. 2F5 was isolated back in the 90's (for example, see http://tinyurl.com/bm3sn5 from 1994). Since then, 2F5 has gone through a few clinical trials as potential HIV therapy, proving safe but not too effective (it's not in any more trials that I am aware of).

Then, in 6-2005, Barton Haynes published in SCIENCE ( http://tinyurl.com/b28drv ) that 2F5 (and 4E10) binds to the Phospholipid Cardiolipin. Shortly thereafter, Haynes became CHAVI Director and got a $15mm Grant from The Gates Foundation (CAVD) for “Broadly Reactive Neutralizing Antibodies: Novel Strategies for Vaccine Design”.

Sometime in 2005-2006, Dr. Haynes became interested in Peregrine’s Anti-PS mabs discovered by Dr. Philip Thorpe (UTSW), because in 2-2007 Haynes added this to his Duke CAVD-Missions webpage ( http://tinyurl.com/674936 ): “Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine (PS) autoantibodies to protection from HIV infection”. Several of Haynes’ CAVD update reports mentioned ongoing anti-lipid studies, but then in his 9-22-08 CAVD PROGRESS REPORT, this popped up: “The team has recently found that non-pathogenic anti-lipid antibodies that do not require B2GP1 for lipid binding do prevent HIV-1 & SHIV-SF162P3 (and all R5 HIVs tested) from infecting PBMC in vitro..."
http://www.cavd.org/grantees/pages/progressAbstracts_Haynes.aspx

And, of course, the next major revelation was the Haynes/Moody “Anti-Lipid” presentation at AIDS-VACCINE’08:
10-14-08: “The AIDS Vaccine 2008 Conference”, CapeTown, So.Africa
...Duke’s B.Haynes & T.Moody present (Oral Abstract) Anti-PS data for 1st time publicly:
“We studied a panel of human anti-lipid mAbs from autoimmune disease patients and healthy controls. 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."
http://tinyurl.com/7dnmpe

If you’d like to persue this intriguing relationship between “the rare, naturally-occuring broadly-neutralizing human mabs 2F5 & 4E10” and the “broadly-neutralizing anti-lipid antibodies” from the PPHM-Duke-HIV-Collab. (ex: PGN632) and presented by Moody/Haynes at AIDS-VACCINE’08 last October in CapeTown
READ THIS POST ON http://anti-ps.blogspot.com:
“CHAVI Hypothesis Bolstered by Recent Findings”
http://anti-ps.blogspot.com/2009/02/chavi-hypothesis-bolstered-by-recent.html

Oh, how does 2F5 stack up against PGN632/11.31 (from the PPHM-Duke-Collab.) when it comes to INHIBITING HIV-1 in-vitro? Recall this Moody/Haynes/Montefiori AIDS-VAC’08 slide (see below – thanks to Mojo: http://tinyurl.com/bxs4tk 1-17-09), that compares 2F5 with PGN632/11.31, in their ability to neutralize HIV. In a nutshell, PGN632/11.31 blew away the ‘Tri-Mab’ of 2F5, b12, and 2G12 – many more times more potent [ex, SHIV-SP162P3: .06/PGN632 vs. 1.5/TriMab].
The key slide….
MOODY/HAYNES AIDS’08/CAPETOWN 10-14-08 (courtesy Dr. Ralph Pantophlet):
'Anti-Lipid Antibodies Inhibit HIV-1 Primary Isolates With Greater Breadth than 2F5, 2G12 and b12'

FOR MORE ON THE APPARENT POWER OF PGN632 TO INHIBIT HIV, RE-READ THIS POST:
Dr. Ralph Pantophlet’s summary of T.Moody’s Talk, incl. 2 PGN632=11.31 test data graphs: http://tinyurl.com/7w4udz

= = = = = = = = = = =
Finally, it turns out that Monday’s Duke article about 2F5 is about the PUBLISHING (in Jrnl-Virology) of the data originally POSTER-PRESENTED by Duke’s Dr. Georgia Tomaras [CHAVI, Immune Monitoring Core] last October at the AIDS-VACCINE’08 Conference.

Here’s the 10-2008 AIDS-VAC’08 Poster Presentation link:
http://www.hivvaccineenterprise.org/_dwn/forms/Final%20Abstract%20Book.pdf
Go to Abstract #P04-32, pg. 111 (PDF pg.132):
“2F5-Like Antibody Identified from an HIV-Infected Patient Concurrent with the Dev. of Autoimmune Antibodies”
X Shen, D Montefiori, R Parks, BF Haynes, GT Tomaras (all Duke)

And here’s the JRNL-VIROLOGY Abstract, Published 2-4-09 (ahead-of-print):
”In Vivo gp41 Antibodies Targeting the 2F5 mAb Epitope Mediate HIV-1 Neutralization Breadth”
Shen X, Parks RJ, Montefiori DC, Kirchherr JL, Keele BF, Decker JM, Blattner WA, Gao F, Weinhold KJ, Hicks CB, Greenberg ML, Hahn BH, Shaw GM, Haynes BF, Tomaras GD
http://www.ncbi.nlm.nih.gov/pubmed/19193787

Which, of course, led to the Duke followup article yesterday:
”Duke Scientists Find Rare, Potent Antibody [2F5] to HIV-1”
http://www.dukehealth.org/HealthLibrary/News/duke_scientists_find_rare_potent_antibody_to_hiv_1

It was a perfect example of how news of scientific research developments is distributed…

1) PRESENT*(some news) => 2) MAJOR-PUBLICATION => 3) NEWS(bigger, if worthy).

Now, back to Peregrine… The 1st Paper from the PPHM-Duke-HIV collab. (Moody/Haynes/PGN632) is in Stage1, which occurred 10-2008. We’re awaiting Stage2 & Stage3.

*10-14-08: “The AIDS Vaccine 2008 Conference”, CapeTown, So.Africa
...Duke’s B.Haynes & T.Moody present (Oral Abstract) Anti-PS data for 1st time publicly:
“We studied a panel of human anti-lipid mAbs from autoimmune disease patients and healthy controls. 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."
http://tinyurl.com/7dnmpe