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

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.

• Authors: Guohua Yi, Xiongying Tu, Preeti Bharaj, Hua Guo, Junli Zhang, Premlata Shankar, N Manjunath
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 23 Issue 10 Pg. 1663-70 (Oct 2015) ISSN: 1525-0024 [Electronic] United States
• PMID: 26061648 (Publication Type: Journal Article)

Chemical References

• AIDS Vaccines
• Antibodies, Neutralizing
• Epitopes
• HIV Antibodies
• HIV Envelope Protein gp41
• gp41 protein, Human immunodeficiency virus 1
• Intercellular Adhesion Molecule-1

Topics

• AIDS Vaccines (administration & dosage, immunology)
• Animals
• Antibodies, Neutralizing (blood, chemistry, immunology)
• Antigen Presentation (immunology)
• Disease Models, Animal
• Epitopes (chemistry, genetics, immunology)
• HIV Antibodies (blood, chemistry, immunology)
• HIV Envelope Protein gp41 (genetics, immunology)
• HIV Infections (genetics, immunology)
• HIV-1 (genetics, immunology)
• Humans
• Immunization
• Intercellular Adhesion Molecule-1 (genetics)
• Mice
• Mice, Transgenic
• Models, Molecular
• Protein Binding (immunology)
• Protein Conformation
• Rhinovirus (immunology)