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    Chimeric Rhinoviruses Displaying MPER Epitopes Elicit Anti-HIV Neutralizing Responses

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    Genre
    Journal Article
    Date
    2013-09-06
    Author
    Yi, G
    Lapelosa, M
    Bradley, R
    Mariano, TM
    Dietz, DE
    Hughes, S
    Wrin, T
    Petropoulos, C
    Gallicchio, E
    Levy, RM
    Arnold, E
    Arnold, GF
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    Subject
    AIDS Vaccines
    Amino Acid Sequence
    Animals
    Antibodies, Neutralizing
    Antibodies, Viral
    Epitopes
    Guinea Pigs
    HIV Envelope Protein gp41
    HIV Infections
    HIV-1
    HeLa Cells
    Humans
    Male
    Molecular Sequence Data
    Peptide Fragments
    Peptide Library
    Rhinovirus
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    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5373
    
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    DOI
    10.1371/journal.pone.0072205
    Abstract
    Background:The development of an effective AIDS vaccine has been a formidable task, but remains a critical necessity. The well conserved membrane-proximal external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial targets for AIDS vaccine development, as it has the necessary attribute of being able to elicit antibodies capable of neutralizing diverse isolates of HIV.Methodology/Principle Findings:Guided by X-ray crystallography, molecular modeling, combinatorial chemistry, and powerful selection techniques, we designed and produced six combinatorial libraries of chimeric human rhinoviruses (HRV) displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1, connected to an immunogenic surface loop of HRV via linkers of varying lengths and sequences. Not all libraries led to viable chimeric viruses with the desired sequences, but the combinatorial approach allowed us to examine large numbers of MPER-displaying chimeras. Among the chimeras were five that elicited antibodies capable of significantly neutralizing HIV-1 pseudoviruses from at least three subtypes, in one case leading to neutralization of 10 pseudoviruses from all six subtypes tested.Conclusions:Optimization of these chimeras or closely related chimeras could conceivably lead to useful components of an effective AIDS vaccine. While the MPER of HIV may not be immunodominant in natural infection by HIV-1, its presence in a vaccine cocktail could provide critical breadth of protection. © 2013 Yi et al.
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    Public Library of Science (PLoS)
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    PLoS ONE
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    http://dx.doi.org/10.34944/dspace/5355
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