Potent Immune Responses in Rhesus Macaques Induced by Nonviral Delivery of a Self-amplifying RNA Vaccine Expressing HIV Type 1 Envelope With a Cationic Nanoemulsion

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 m...

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Bibliographic Details
Published in:The Journal of infectious diseases 2015-03, Vol.211 (6), p.947-955
Main Authors: Bogers, Willy M., Oostermeijer, Herman, Mooij, Petra, Koopman, Gerrit, Verschoor, Ernst J., Davis, David, Ulmer, Jeffrey B., Brito, Luis A., Cu, Yen, Banerjee, Kaustuv, Otten, Gillis R., Burke, Brian, Dey, Antu, Heeney, Jonathan L., Shen, Xiaoying, Tomaras, Georgia D., Labranche, Celia, Montefiori, David C., Liao, Hua-Xin, Haynes, Barton, Geall, Andrew J., Barnett, Susan W.
Format: Article
Language:English
Subjects:
Adaptive Immunity
AIDS Vaccines - administration & dosage
AIDS Vaccines - immunology
Animals
Animals, Outbred Strains
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Cations
Cells, Cultured
Emulsions
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
HIV Infections - immunology
HIV Infections - prevention & control
HIV-1 - immunology
HIV/AIDS
Immunity, Cellular
Macaca mulatta
Major and Brief Reports
Male
RNA, Viral - immunology
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Summary: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 selfamplifying 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 (50µg) of formulated self-amplifying mRNA is safe and immunogenic.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiu522