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
Open accessAbstract
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 µg) of formulated self-amplifying mRNA is safe and immunogenic.
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For prophylactic mRNA vaccines, such T cell responses have, to the authors' best knowledge, only been detected in NHPs after vaccination with self-amplifying mRNA but not with non-amplifying mRNA.
“and have, to our best knowledge, for prophylactic mRNA vaccines only been detected in NHPs after vaccination with self-amplifying mRNA31 but not with non-amplifying mRNA.”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [31]
Several preclinical studies have delivered mRNA vaccines encoding HIV proteins using multiple delivery vehicles, but they have had varied success.
“Several preclinical studies have delivered mRNA vaccines encoding HIV proteins using multiple delivery vehicles, including cationic nanoemulsions109,161, DOTAP/DOPE liposomes162, polymers84,163,164 and ionizable LNPs165,166, but they have had varied success.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [161]
Novel antigens are necessary to effectively target HIV in addition to potent delivery vehicles.
“These studies suggest that novel antigens are necessary to effectively target HIV in addition to potent delivery vehicles.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [161]
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Self-citation
- Authors
- Bogers, W. M., Oostermeijer, H., Mooij, P., Koopman, G., Verschoor, E. J., Davis, D., Ulmer, J. B., Brito, L. A., Cu, Y., Banerjee, K., Otten, G. R., Burke, B., Dey, A., Heeney, J. L., Shen, X., Tomaras, G. D., Labranche, C., Montefiori, D. C., Liao, H.-X., Haynes, B., Geall, A. J., & Barnett, S. W.
- Affiliations
- Biomedical Primate Research Centre (NL)
- University of Cambridge (GB)
- Duke University (US)
- Duke Medical Center (US)
- Corresponding author
- Bogers, W. M.
- ORCID
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-09-18
- Volume
- 211
- Issue
- 6
- Pages
- 947-955
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC4416123
- OpenAlex
- W2162541845
- Cited by
- 181
- References
- 53
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 33 · 2021: 27 · 2020: 22 · 2019: 15 · 2018: 12 · 2017: 10 · 2016: 9 · 2015: 7 · 2014: 3
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (PO1 AI066287-02)
- National Institute of Allergy and Infectious Diseases (P01AI066287)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- self-amplifying mRNA vaccine, cationic nanoemulsions, rhesus monkeys, cell-mediated immunity, neutralizing antibodies, MF59 adjuvant, vaccine safety, immunogenicity, HIV vaccine
- MeSH terms
- Animals, Antibodies, Viral, Cations, Cells, Cultured, Emulsions, Immunity, Cellular, Macaca mulatta, Male, RNA, Viral, HIV-1, HIV Infections, AIDS Vaccines, Animals, Outbred Strains, env Gene Products, Human Immunodeficiency Virus, Adaptive Immunity, Antibodies, Neutralizing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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