Avid Bioservices Inc (CDMO)

[jazzbeerman]

jess,





I looked back, sorry - it wasn't you who downplayed Bavi's role in the work. It was "moby", saying it "only referred to Bavi in the context as a stain control."

As for Bavi, yes, it was indeed bavi/2AG4 that was used by Haynes in the microparticle work that was published in Virology, which showed how the exposed PS on microparticles is responsible for blunting the function of the immune cells that would ideally fight the virus, and that Bavi (2AG4) itself masks/binds the exposed PS.

Interestingly.....Bavi was not mentioned in the paper, but reading the details of the same work in the patent application shows that it was indeed Bavi. Here are those details -


The following graphs (re: microparticle counts vs: viral load) were in the paper, and the paper discussed the microparticles being responsible..., and counting how the microparticles ramped up right before (allowing) the virus to ramp up..., since the microparticles expose PS...







The patent application contains the 'same' graph (re: microparticle counts vs: viral load) - with the following caption:



Figure 15. Microparticles expressing phosphatidylserine in AHI Plasma. Various time points of panel 6246 (21 days before viral load was detected, day - 21, and 7, 11 and 14 days after viral load was measured to be > 100 copies/ml) were assayed by flow cytometry for the presence of microparticles stained with anti-phosphatidylserine antibodies (2aG4). As a control, plasma from a normal, uninfected blood bank donor was also assayed in the same manner.

..........

more info -

Thus, the massive apoptosis that occurs with acute HIV infection with resulting release of TRAIL, mediation of apoptosis via FAS-FASL interactions, and release of PS containing viral and other particles, all conspire to initially immuno suppress the host, preventing rapid protective B cell responses. Next, flow cytometry phenotypic analysis of the microparticles in AHI sample 6246-15 was performed (Fig. 10). Fig. 11 shows the forward and side scatter of background with phosphate buffered saline, pH 7, purified microparticles from staurosporine treated Jurkat T cells, and the microparticles in patient 6246 plasma on day 11 at the time of peak viremia. Fig. 11 shows the microparticles in plasma with each panel counted for 2 minutes. Fig. 12 shows the phenotype of either purified Jurkat microparticles (pMP) or patient 6246 MP and shows that the microparticles can be phenotypically analyzed and that the AHI patient microparticles are 78.6 % CD3+, 53% CD45 +. CD45 is a surface molecule of T and monocyte cells that is not incorporated into HIV virions (Esser et al, J. Virol. 75:6173-6182 (2001)). Thus, about one half of the microparticles are likely virions in Fig. 12 and one half of the particles are apoptotic particles from HIV-uninfected cells or do not contain HIV genetic material. Of importance, most of the microparticles from patient 6246 are phosphatidylserine (PS) positive (Fig. 13). Similarly, HIV-infected cells are PS+, as shown in Fig. 14.


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Now that I've gone back to clarify this, it's become obvious to me why Haynes didn't mention Bavi, or even that the counting of the microparticles discussed in the paper were counted via anti-PS / (Bavi), while it IS mentioned, repeatedly, in the patent applications.

IMHO, because it's an important topic for a separate paper. I base that opinion on all the recently published patent applications containing the BAVI / HUMANIZED BAVI / TARVI / IS1 discussions/info...

j