title: Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey, United States of America ; Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey, United States of America.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yi
authors.forename: Mauro
authors.initials: M
authors.lastname: Lapelosa
authors.forename: Rachel
authors.initials: R
authors.lastname: Bradley
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mariano
authors.forename: Denise Elsasser
authors.initials: DE
authors.lastname: Dietz
authors.forename: Scott
authors.initials: S
authors.lastname: Hughes
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Chris
authors.initials: C
authors.lastname: Petropoulos
authors.forename: Emilio
authors.initials: E
authors.lastname: Gallicchio
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Levy
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
authors.forename: Gail Ferstandig
authors.initials: GF
authors.lastname: Arnold
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006168:Guinea Pigs; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D019151:Peptide Library; D012229:Rhinovirus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D019151:Peptide Library; C514787:gp41 protein, Human immunodeficiency virus 1
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