Broad Neutralization of Primary Isolates
This is the experiment to determine the breath of PI virus neutralization elicited by FC immunogens!
The sensitivity of a panel of representative PI viruses from five prevalent and geographically diverse phylogenetic clades also called subtypes- groups of related HIV isolates classified according to their degree of genetic similarity ( such as of their envelope protein ). There are currently two groups of HIV-1 isolates, M and O. M consists of at least nine clades, A through I. Group O may also consist of a number of clades. are pictured below:
Monocytotropic (non-SI;NSI) and T lymphocytotropic (SI viruses) from North America and Europe (clade B), Africa (clades A and D), Thailand (clades B and E), and India (clade C). FC immunogen = black squares
Of the 24 PI viruses tested, how many were able to be neutralized by FC sera elicited by a functioning clade B envelope protein? Answer 23
Interpretation? despite the sequence diversity among these isolates, most were similarly sensitive to neutralization by FC vaccine sera.
But wait, what about the one isolate (92RW008) that failed to attain >50% neutralization and two others (93IN904 and 92UG024) showed limited neutralization beyond 50%?
Answer These further indicate that FC immunogens target primarily viral rather than cellular determinants
Interpretation of the FI sera results in the figure above? Answer FI sera were uniformly unable to neutralize these heterologous PI viruses, in keeping with the failure of rgp 120 immunogens, too.
So, what does the broad and uniform neutralization of diverse PI viruses suggest? Answer Critical determinants presented by FC immunogens are highly conserved and may be intimately tied to the basic functioning of the envelope protein in binding and fusion.
What's next? Click to define the molecular target for neutralization by FC vaccines
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