Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape

Gromowski, Gregory D.; Roehrig, John T.; Diamond, Michael S.; Lee, J. Ching; Pitcher, Trevor; Barrett, Alan D.T.

doi:10.1016/j.virol.2010.06.044

Cited by 43 publications

(49 citation statements)

References 39 publications

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“…These residues could be further investigated by mutation to understand how mutation giving an impact on the binding affinity either enhance or harm the binding activity. Three residues of the binding sites as reported by Lok [14] were further studied by Gromowski [7]. Mutation of these three residues harmed the binding of antibody and domain III.…”

Section: Resultsmentioning

confidence: 98%

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Exploration of Residue Binding Energy of Potential Ankyrin for Dengue Virus II from MD Simulations

Chong¹,

Zain²,

Rahman³

et al. 2015

Proceedings of the 3rd International Conference on Computation for Science and Technology

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Abstract:Computational approach was employed to evaluate the binding activity of potential ankyrin and domain III of the envelope protein of dengue virus II. Ankyrin serves as an alternative to antibody due to several advantages. Both the ankyrin and domain III were docked using Z-dock protocol in Discovery Studio suite of programme. The docked complex was simulated under GPU-accelerated workstation for long time scale and followed by binding free energy calculation using Molecular Mechanics-Poisson-Boltzmann Surface Area/Generalized Born Solvent Area (MM-PBSA/GBSA). Decomposed binding free energy located the possible hot spots on ankyrin and also domain III. Several amino residues on ankyrin were observed to be potent mutation points by comparing the energy from snapshots extracted during 3 ns and 6-10 ns.

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Section: Resultsmentioning

confidence: 98%

“…There is an immunoglobulin-like fold which is a common structure as cell receptor and it was observed to project further away from both domains I and domain II [7]. Domain III was found that respond to the antibody neutralisation as well [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Exploration of Residue Binding Energy of Potential Ankyrin for Dengue Virus II from MD Simulations

Chong¹,

Zain²,

Rahman³

et al. 2015

Proceedings of the 3rd International Conference on Computation for Science and Technology

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“…This approach was used successfully with a recombinant ED3 and effectively removed the amino acid side chains, while retaining the native ED3 conformation (Gromowski et al, 2010). The WT and three mutant ICs (K305A, K310A and P384A) were transcribed in vitro and electroporated into Vero cells (African green monkey kidney).…”

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confidence: 99%

Functional analysis of dengue virus (DENV) type 2 envelope protein domain 3 type-specific and DENV complex-reactive critical epitope residues

Pitcher

Sarathy

Matsui

et al. 2015

Journal of General Virology

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The dengue virus (DENV) envelope protein domain 3 (ED3) is the target of potent virus neutralizing antibodies. The DENV-2 ED3 contains adjacent type-specific and DENV complex-reactive antigenic sites that are composed of a small number of residues that were previously demonstrated to be critical for antibody binding. Site-directed mutagenesis of a DENV-2 16681 infectious clone was used to mutate critical residues in the DENV-2 type-specific (K305A and P384A) and DENV complex-reactive (K310A) antigenic sites. The K305A mutant virus multiplied like the parent virus in mosquito and mammalian cells, as did the P384A mutant virus, which required a compensatory mutation (G330D) for viability. However, the K310A mutant virus could not be recovered. The DENV-2 type-specific critical residue mutations K305A and P384A+G330D reduced the ability of DENV-2 type-specific, but not DENV complex-reactive, mAbs to neutralize virus infectivity and this was directly correlated with mAb binding affinity to the rED3 mutants.The disease dengue (DEN) is caused by four serologically and genetically related dengue viruses (DENVs) termed DENV-1, -2, -3 and -4. The DENV envelope (E) protein is composed of three domains: E protein domain I (ED1) is the central domain, ED2 is the dimerization domain and contains the conserved fusion loop, and ED3 is the putative receptor-binding domain (Modis et al

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“…Mouse monoclonal antibodies (MAbs) that neutralize DENV map to all three domains (35). However, the monoclonal antibodies with the strongest neutralization are serotype specific and map to EDIII (37)(38)(39)(40)(41)(42), which is a region of ϳ100 amino acids that folds into an immunoglobulin-like domain and has been implicated in host receptor binding (43). The minor surface glycoprotein, prM/M, plays a role in proper folding of E and particle assembly and is present as uncleaved prM in the immature particle and partly or fully cleaved M in the mature particle (44).…”

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confidence: 99%

An Alphavirus Vector-Based Tetravalent Dengue Vaccine Induces a Rapid and Protective Immune Response in Macaques That Differs Qualitatively from Immunity Induced by Live Virus Infection

White

Sariol

Mattocks

et al. 2013

J Virol

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Despite many years of research, a dengue vaccine is not available, and the more advanced live attenuated vaccine candidate in clinical trials requires multiple immunizations with long interdose periods and provides low protective efficacy. Here, we report important contributions to the development of a second-generation dengue vaccine. First, we demonstrate that a nonpropagating vaccine vector based on Venezuelan equine encephalitis virus replicon particles (VRP) expressing two configurations of dengue virus E antigen (subviral particles [prME] and soluble E dimers [E85]) successfully immunized and protected macaques against dengue virus, while antivector antibodies did not interfere with a booster immunization. Second, compared to prME-VRP, E85-VRP induced neutralizing antibodies faster, to higher titers, and with improved protective efficacy. Third, this study is the first to map antigenic domains and specificities targeted by vaccination versus natural infection, revealing that, unlike prME-VRP and live virus, E85-VRP induced only serotype-specific antibodies, which predominantly targeted EDIII, suggesting a protective mechanism different from that induced by live virus and possibly live attenuated vaccines. Fourth, a tetravalent E85-VRP dengue vaccine induced a simultaneous and protective response to all 4 serotypes after 2 doses given 6 weeks apart. Balanced responses and protection in macaques provided further support for exploring the immunogenicity and safety of this vaccine candidate in humans.

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Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape

Cited by 43 publications

References 39 publications

Exploration of Residue Binding Energy of Potential Ankyrin for Dengue Virus II from MD Simulations

Exploration of Residue Binding Energy of Potential Ankyrin for Dengue Virus II from MD Simulations

Functional analysis of dengue virus (DENV) type 2 envelope protein domain 3 type-specific and DENV complex-reactive critical epitope residues

An Alphavirus Vector-Based Tetravalent Dengue Vaccine Induces a Rapid and Protective Immune Response in Macaques That Differs Qualitatively from Immunity Induced by Live Virus Infection

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