Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice

Guohua Yi, Xiongying Tu, Preeti Bharaj, Hua Guo, Junli Zhang, Premlata Shankar, N. Manjunath

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Attempts at eliciting neutralizing antibodies against human immunodeficiency virus (HIV)-1 have generally failed. Computationally designed epitope-scaffold platforms allow transplantation of structural epitopes to scaffold proteins. Human rhinovirus (HRV) allows such engrafting of HIV-1 epitopes on the surface scaffold proteins. However, since HRV infects only humans and great apes, the efficacy of chimeric HRV-based live viral vaccines is difficult to assess in animal models. Here, we used human ICAM-1 transgenic (hICAM-1 Tg) mice that support productive HRV infection to assess the efficacy of chimeric HRV expressing the HIV-1 membrane proximal external region (MPER) epitope, 4E10. Intranasal immunization with chimeric HRV in transgenic mice effectively induced antibodies that recognized 4E10 peptide as well as HIV-1 Env trimer. Importantly, the immunized mouse sera were able to neutralize HIV strains including those belonging to clades B and C. Moreover, intranasal immunization could bypass pre-existing immunity to HRV. Thus, chimeric HRV appears to provide a viable vaccine vehicle for HIV-1 immunization in humans.

Original languageEnglish (US)
Pages (from-to)1663-1670
Number of pages8
JournalMolecular Therapy
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Rhinovirus
Intercellular Adhesion Molecule-1
Neutralizing Antibodies
Transgenic Mice
HIV-1
Epitopes
Membranes
Immunization
Viral Vaccines
Hominidae
Immunity
Membrane Proteins
Vaccines
Animal Models
Transplantation
HIV

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice. / Yi, Guohua; Tu, Xiongying; Bharaj, Preeti; Guo, Hua; Zhang, Junli; Shankar, Premlata; Manjunath, N.

In: Molecular Therapy, Vol. 23, No. 10, 01.10.2015, p. 1663-1670.

Research output: Contribution to journalArticle

Yi, Guohua ; Tu, Xiongying ; Bharaj, Preeti ; Guo, Hua ; Zhang, Junli ; Shankar, Premlata ; Manjunath, N. / Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice. In: Molecular Therapy. 2015 ; Vol. 23, No. 10. pp. 1663-1670.
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