Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 211, Issue 6, Pages 947-955Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu522
Keywords
self-amplifying mRNA; HIV; vaccine; antibodies; T cells
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Funding
- National Institutes of Health [5 PO1 AI066287-02]
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Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platform is based on a synthetic, self-amplifying mRNA delivered by a nonviral delivery system. The safety and immunogenicity of an HIV SAM vaccine encoding a clade C envelope glycoprotein formulated with a cationic nanoemulsion (CNE) delivery system was evaluated in rhesus macaques. The HIV SAM vaccine induced potent cellular immune responses that were greater in magnitude than those induced by self-amplifying mRNA packaged in a viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant, anti-envelope binding (including anti-V1V2), and neutralizing antibody responses that exceeded those induced by the VRP vaccine. These studies provide the first evidence in nonhuman primates that HIV vaccination with a relatively low dose (50 mu g) of formulated self-amplifying mRNA is safe and immunogenic.
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