Generation and characterization of a live, bivalent vaccine against human immunodeficiency virus and Ebola virus
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Date
2016
Authors
Mendoza, Emelissa J.
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Abstract
Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome by targeting and destroying CD4+ T cells via its Envelope protein (Env), while Ebola virus (EBOV) causes a lethal hemorrhagic fever and targets antigen presenting cells (APCs) via its glycoprotein (GP). There are no licensed vaccines for either virus, posing a problem particularly in Africa, where succumbing to EBOV or HIV is a grim reality. We hypothesized that a replication-competent HIV expressing GP as a replacement for Env will redirect the virus from CD4+ T cells toward antigen presenting cells and act as a live, bivalent vaccine to induce cellular and humoral immune responses against both pathogens, and confer protection against a lethal EBOV challenge in mice. Recombinant HIV-1 molecular clones containing different truncations of the GP gene to replace HIV gp120 were generated and used to rescue three GP-expressing vaccines, HIV-EBOV, HIV-EBOVΔ1, and HIV-EBOVΔ2. These demonstrated tropism for the monocyte cell line, THP-1, and decreased tropism for the CD4+ T cell line, SupT1. While all vaccines induced HIV p24- and GP-specific IFN-γ-secreting T cell responses, HIV-EBOVΔ1 and HIV-EBOVΔ2 induced the most robust responses at 21 days post-vaccination (dpv), respectively. While all vaccines induced total anti-p24 and anti-GP IgG responses, HIV-EBOVΔ1 induced the most robust responses at 42 dpv. HIV-EBOVΔ1 demonstrated the highest protective efficacy against lethal EBOV challenge, followed by HIV-EBOVΔ2 and HIV-EBOV, providing 83%, 67%, and 50% survival in mice, respectively. HIV-EBOVΔ1 shows promise as a protective vaccine against EBOV, but may require further optimization and characterization regarding its mechanism of action and ability to protect against HIV.
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Keywords
Vaccine, HIV, Ebola virus, Immunology