Cited by 103HIV Research and TreatmentSARS-CoV-2 and COVID-19 ResearchImmunotherapy and Immune Responses

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques

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Pardi, Norbert, LaBranche, Celia C., Ferrari, Guido, Cain, Derek W., Tombácz, István, Parks, Robert J., Muramatsu, Hiromi, Mui, Barbara L. +10 more·2019·Molecular Therapy - Nucleic Acids

Abstract

Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize the immune responses induced by nucleoside-modified and purified mRNA-lipid nanoparticle (mRNA-LNP) vaccines encoding the clade C transmitted/founder HIV-1 envelope (Env) 1086C. Intradermal vaccination with nucleoside-modified 1086C Env mRNA-LNPs elicited high levels of gp120-specific antibodies in rabbits and rhesus macaques. Antibodies generated in rabbits neutralized a tier 1 virus, but no tier 2 neutralization activity could be measured. Importantly, three of six non-human primates developed antibodies that neutralized the autologous tier 2 strain. Despite stable anti-gp120 immunoglobulin G (IgG) levels, tier 2 neutralization titers started to drop 4 weeks after booster immunizations. Serum from both immunized rabbits and non-human primates demonstrated antibody-dependent cellular cytotoxicity activity. Collectively, these results are supportive of continued development of nucleoside-modified and purified mRNA-LNP vaccines for HIV. Optimization of Env immunogens and vaccination protocols are needed to increase antibody neutralization breadth and durability.

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Crossref · 10.1016/j.omtn.2019.03.003

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  • 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.”
  • 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.”

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Authors
Pardi, N., LaBranche, C. C., Ferrari, G., Cain, D. W., Tombácz, I., Parks, R. J., Muramatsu, H., Mui, B. L., Tam, Y. K., Karikó, K., Polacino, P., Barbosa, C. J., Madden, T. D., Hope, M. J., Haynes, B. F., Montefiori, D. C., Hu, S.-L., & Weissman, D.
Affiliations
  • University of Pennsylvania (US)
  • Duke Medical Center (US)
  • Duke University (US)
  • Acuitas Therapeutics (Canada) (CA)
  • BioNTech (Germany) (DE)
  • University of Washington (US)
Corresponding author
  • Pardi, Norbert
  • Weissman, Drew
Venue
Molecular Therapy - Nucleic Acids
Publisher
Elsevier BV
Published
2019-04
Volume
15
Pages
36-47
ISSN
2162-2531 (ISSN-L)
OpenAlex
W2924788224
Cited by
103
References
59
Citations by year
2026: 4 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 17 · 2021: 26 · 2020: 14 · 2019: 2
FWCI
8.26
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Allergy and Infectious Diseases (UM1 AI100645, HHSN272201100016C)
  • Bill and Melinda Gates Foundation
  • National Institutes of Health (P51 OD010425)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
HIV-1 vaccine, nucleoside-modified mRNA, mRNA-LNP vaccine, HIV-1 envelope glycoprotein, neutralizing antibodies, antibody-dependent cellular cytotoxicity, intradermal vaccination, booster vaccination, antibody persistence, rabbits, rhesus monkeys

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