These results demonstrate that the construction of such chimeric proteins can provide enhanced exposure of conserved epitopes in the HIV Env gp41 and may represent a novel vaccine design strategy for inducing broadly neutralizing antibodies against HIV.
Time-of-flight secondary ion mass spectrometry (ToF-SIMS) fragmentation patterns, in conjunction with multivariate statistics, demonstrated enhanced exposure of the lipase's catalytic domain, specifically the histidine group responsible for activity, when CalA was adsorbed on hydrophilic silica.
Using a naturally occurring HIV-1 Envelope (Env) variant as a template, we sought to identify features of Env that would enhance exposure of conserved HIV-1 epitopes.Within a cohort study of high-risk women in Mombasa, Kenya, we previously identified a subtype A HIV-1 Env variant in one participant that was unusually sensitive to neutralization.
More importantly, these experiments demonstrated that nanosuspension formulations can be used to enhance exposure of compounds with low solubility and poor pharmacokinetic characteristics for early decision-making in a drug discovery environment.
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Blish et al. have shown that introduction of two mutations (T569A and I675V) into gp41 results in significantly enhanced exposure of the conserved neutralization epitopes in MPER and renders the HIV-1 mutants 360- and 180-fold more susceptible to 2F5 and 4E10, respectively [19].
Oligomers of glutathionylated apo-SOD1 were also probed with C4F6 to determine whether this modification induces structural rearrangements that enhance exposure of the disease-specific epitope.
Enhanced exposure of the disease-linked epitope in non-native SOD1 oligomers supports a cytotoxic role for these assemblies, in parallel with previous findings directly demonstrating the toxicity of small oligomers of Aβ and α-synuclein in models of Alzheimer's disease and Parkinson's disease, respectively.
Alternate methods to enhance exposure to continuity of care issues within the constraints of existing residency training programs are needed.
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