Avid Bioservices Inc (CDMO)

[jazzbeerman]

jess, Bart Haynes words are a little less conservative -


Method of inducing neutralizing antibodies to human immunodeficiency virus


Bart Haynes:

* "IS1 is an antibody that can be safely used as a therapeutic Mab for treatment of HIV infected subjects"


http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=2&p=1&f=G&l=50&d=PG01&S1=%28%22haynes+barton%22.IN.%29&OS=in/%22haynes+barton%22&RS=IN/%22haynes+barton%22


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Bart Haynes:

* "both IS1 and IS4 neutralized 7/7 primary isolates tested"


* "both IS1 and IS4 Mabs reacted strongly with the surface of virus infected T cells."




Supported by the Center for HIV/AIDS Vaccine Immunology AI067854,
CHAVI 005 protocol.

http://www.hivvaccineenterprise.org/_dwn/Late_Breaker_Abstracts.pdf


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Induction of Plasma (TRAIL), TNFR-2, Fas Ligand and Plasma Microparticles After
HIV-1 Transmission: Implications for HIV-1 Vaccine Design



Bart Haynes:

* "Significant plasma TRAIL elevations occurred a mean of 7.2 days before the
peak of plasma viral load (VL), while TNFR2, Fas ligand and microparticle elevations
occurred coincident with maximum VL. Microparticles have been previously shown to
mediate immunosuppressive effects on T cells and macrophages. We found that T cell
apoptotic microparticles also potently suppressed in vitro IgG and IgA antibody
production by memory B cells."


* "Microparticles (MPs) are small
membrane-bound vesicles that are released from the surface of apoptotic cells by
exocytic or budding processes; as such, MPs bear cell surface markers and can bind
annexin V because of the expression of phosphatidylserine"


* "MPs have immunomodulatory activities and can promote immune
cell death; exosomes are also immunologically active, can suppress immune responses
(20,34,42,55), and have been reported elevated in chronic HIV-1 "


* "suppression of immune responses can be mediated by T cell MPs (32,34,35).
CXCR4+ and CCR5+ MPs can transfer co-receptors to co-receptor negative cells, making
them susceptible to infection by HIV-1 (48,57). Phagocytosis of MPs by macrophages
releases TGF-beta, prostaglandin E2 and IL-10 that can inhibit antigen-specific T and B cell
responses (20,35,42). In this regard, Estes et al. have shown dramatic increases in lymph
node TGF-beta and IL-10 on day 12 following SIV infection (22). Importantly, we have
demonstrated that PBMC and tonsillar cell MPs can directly inhibit memory B cell activation"


* "both Fas ligand and TRAIL are incorporated into MPs (37,53). Fas ligand
expressing MPs can directly induce apoptosis in nearby cells (20,37,53), and activated T cells
can be the target of Fas ligand-mediated proapoptotic microvesicles "


* "it is likely that MPs are responsible for the observed B
cell suppressive activity seen in vitro in Figure 8. In the setting of HIV-1 infection where
both activation and apoptosis occur, however, MPs and exosomes may act concomitantly,
with exosomes suppressing immune responses (2,7,15,61), and MPs contributing to both
immune suppression and cell death"


http://jvi.asm.org/cgi/content/full/82/15/7700?view=long&pmid=18508902


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j