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mRNA technology for the prevention and treatment of HIV-1 infection

  • Bekker, L. G. et al. HIV infection. Nat. Rev. Dis. Primers 9, 42 (2023).

    Article 

    Google Scholar
     

  • Montagnier, L. Historical essay. A history of HIV discovery. Science 298, 1727–1728 (2002).

    Article 

    Google Scholar
     

  • Chen, L. et al. Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat. Commun. 9, 4585 (2018).

    Article 

    Google Scholar
     

  • Landovitz, R. J., Scott, H. & Deeks, S. G. Prevention, treatment and cure of HIV infection. Nat. Rev. Microbiol. 21, 657–670 (2023).

    Article 

    Google Scholar
     

  • Gbadamosi, S. O., Trepka, M. J., Dawit, R., Jebai, R. & Sheehan, D. M. A systematic review and meta-analysis to estimate the time from HIV infection to diagnosis for people with HIV. AIDS Rev. 24, 32–40 (2022).


    Google Scholar
     

  • Bartlett, J. A. & Shao, J. F. Successes, challenges, and limitations of current antiretroviral therapy in low-income and middle-income countries. Lancet Infect. Dis. 9, 637–649 (2009).

    Article 

    Google Scholar
     

  • Grinsztejn, B. et al. Third-line antiretroviral therapy in low-income and middle-income countries: ACTG A5288, a prospective strategy study. Lancet HIV 6, e588–e600 (2019).

    Article 

    Google Scholar
     

  • Haynes, B. F. et al. Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies. Nat. Rev. Immunol. 23, 142–158 (2023).

    Article 

    Google Scholar
     

  • Sok, D. & Burton, D. R. Recent progress in broadly neutralizing antibodies to HIV. Nat. Immunol. 19, 1179–1188 (2018).

    Article 

    Google Scholar
     

  • Goo, L., Chohan, V., Nduati, R. & Overbaugh, J. Early development of broadly neutralizing antibodies in HIV-1-infected infants. Nat. Med. 20, 655–658 (2014).

    Article 

    Google Scholar
     

  • Escolano, A. et al. Sequential immunization elicits broadly neutralizing anti-HIV-1 antibodies in Ig knockin mice. Cell 166, 1445–1458.e12 (2016).

    Article 

    Google Scholar
     

  • Steichen, J. M. et al. Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Science 384, eadj8321 (2024).

    Article 

    Google Scholar
     

  • Willis, J. R. et al. Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans. Science 389, eadr8382 (2025).

    Article 

    Google Scholar
     

  • Kelsoe, G. & Haynes, B. F. Host controls of HIV broadly neutralizing antibody development. Immunol. Rev. 275, 79–88 (2017).

    Article 

    Google Scholar
     

  • Burton, D. R. & Mascola, J. R. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat. Immunol. 16, 571–576 (2015).

    Article 

    Google Scholar
     

  • Kwong, P. D., Mascola, J. R. & Nabel, G. J. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat. Rev. Immunol. 13, 693–701 (2013).

    Article 

    Google Scholar
     

  • Barouch, D. H. et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys (NHP 13-19). Lancet 392, 232–243 (2018).

    Article 

    Google Scholar
     

  • Barouch, D. H. et al. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science 349, 320–324 (2015).

    Article 

    Google Scholar
     

  • Gray, G. E. et al. Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120-MF59 in adults. N. Engl. J. Med. 384, 1089–1100 (2021).

    Article 

    Google Scholar
     

  • Gray, G. E. et al. Mosaic HIV-1 vaccine regimen in southern African women (Imbokodo/HVTN 705/HPX2008): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Infect. Dis. 24, 1201–1212 (2024).

    Article 

    Google Scholar
     

  • Kay, M. A. AAV vectors and tumorigenicity. Nat. Biotechnol. 25, 1111–1113 (2007).

    Article 

    Google Scholar
     

  • Donsante, A. et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 317, 477 (2007).

    Article 

    Google Scholar
     

  • Nguyen, G. N. et al. A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. Nat. Biotechnol. 39, 47–55 (2021).

    Article 

    Google Scholar
     

  • Wang, D., Zhang, F. & Gao, G. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell 181, 136–150 (2020).

    Article 

    Google Scholar
     

  • Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018).

    Article 

    Google Scholar
     

  • Mu, Z., Haynes, B. F. & Cain, D. W. HIV mRNA vaccines — progress and future paths. Vaccines 9, 134 (2021).

    Article 

    Google Scholar
     

  • Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021).

    Article 

    Google Scholar
     

  • Chaudhary, N., Weissman, D., Whitehead, K. A., Weissman, D. & Whitehead, K. A. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).

    Article 

    Google Scholar
     

  • McGee, J. E. et al. Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency. Nat. Biotechnol. 43, 720–726 (2025).

    Article 

    Google Scholar
     

  • Wu, X. et al. The impact of COVID-19 non-pharmaceutical interventions on HIV care continuum in China: an interrupted time series analysis. Lancet Reg. Health West. Pac. 29, 100569 (2022).


    Google Scholar
     

  • Pardi, N. et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 215, 1571–1588 (2018).

    Article 

    Google Scholar
     

  • Huang, X. et al. Nanotechnology-based strategies against SARS-CoV-2 variants. Nat. Nanotechnol. 17, 1027–1037 (2022).

    Article 

    Google Scholar
     

  • Meulewaeter, S. et al. Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures. J. Control. Rel. 357, 149–160 (2023).

    Article 

    Google Scholar
     

  • Ju, Y. et al. Impact of anti-PEG antibodies induced by SARS-CoV-2 mRNA vaccines. Nat. Rev. Immunol. 23, 135–136 (2023).

    Article 

    Google Scholar
     

  • Goel, R. R. et al. mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern. Science 374, abm0829 (2021).

    Article 

    Google Scholar
     

  • Riddler, S. A. et al. High frequency of chronic urticaria following an investigational HIV-1 BG505 MD39.3 trimer mRNA vaccine in a phase 1, randomized, open-label clinical trial (HVTN 302). Ann. Intern. Med. 178, 963–974 (2025).

    Article 

    Google Scholar
     

  • Parks, K. R. et al. Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial. Sci. Transl. Med. 17, eady6831 (2025).

    Article 

    Google Scholar
     

  • Pardi, N. et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat. Commun. 8, 14630 (2017).

    Article 

    Google Scholar
     

  • Zhang, P. et al. A multiclade env–gagVLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques. Nat. Med. 27, 2234–2245 (2021).

    Article 

    Google Scholar
     

  • Engelman, A. & Cherepanov, P. The structural biology of HIV-1: mechanistic and therapeutic insights. Nat. Rev. Microbiol. 10, 279–290 (2012).

    Article 

    Google Scholar
     

  • Wyatt, R. & Sodroski, J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884–1888 (1998).

    Article 

    Google Scholar
     

  • Julien, J.-P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477–1483 (2013).

    Article 

    Google Scholar
     

  • Stano, A. et al. Dense array of spikes on HIV-1 virion particles. J. Virol. 91, https://doi.org/10.1128/jvi.00415-17 (2017).

  • Mansky, L. M. The mutation rate of human immunodeficiency virus type 1 is influenced by the vpr gene. Virology 222, 391–400 (1996).

    Article 

    Google Scholar
     

  • Leitner, T. & Albert, J. The molecular clock of HIV-1 unveiled through analysis of a known transmission history. Proc. Natl Acad. Sci. USA 96, 10752–10757 (1999).

    Article 

    Google Scholar
     

  • Hemelaar, J. The origin and diversity of the HIV-1 pandemic. Trends Mol. Med. 18, 182–192 (2012).

    Article 

    Google Scholar
     

  • McLaren, P. J. & Carrington, M. The impact of host genetic variation on infection with HIV-1. Nat. Immunol. 16, 577–583 (2015).

    Article 

    Google Scholar
     

  • Simon, V., Bloch, N. & Landau, N. R. Intrinsic host restrictions to HIV-1 and mechanisms of viral escape. Nat. Immunol. 16, 546–553 (2015).

    Article 

    Google Scholar
     

  • Burton, D. R. & Hangartner, L. Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu. Rev. Immunol. 34, 635–659 (2016).

    Article 

    Google Scholar
     

  • Haynes, B. F., Burton, D. R. & Mascola, J. R. Multiple roles for HIV broadly neutralizing antibodies. Sci. Transl. Med. 11, eaaz2686 (2019).

    Article 

    Google Scholar
     

  • Liu, M. et al. Polyreactivity and autoreactivity among HIV-1 antibodies. J. Virol. 89, 784–798 (2015).

    Article 

    Google Scholar
     

  • Yang, G. et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J. Exp. Med. 210, 241–256 (2013).

    Article 

    Google Scholar
     

  • Steichen, J. M. et al. HIV vaccine design to target germline precursors of glycan-dependent broadly neutralizing antibodies. Immunity 45, 483–496 (2016).

    Article 

    Google Scholar
     

  • Jardine, J. G. et al. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458–1463 (2016).

    Article 

    Google Scholar
     

  • Huang, D. et al. B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models. Proc. Natl Acad. Sci. USA 117, 22920–22931 (2020).

    Article 

    Google Scholar
     

  • Bruel, T. et al. Elimination of HIV-1-infected cells by broadly neutralizing antibodies. Nat. Commun. 7, 10844 (2016).

    Article 

    Google Scholar
     

  • Liu, Y., Cao, W., Sun, M. & Li, T. Broadly neutralizing antibodies for HIV-1: efficacies, challenges and opportunities. Emerg. Microbes Infect. 9, 194–206 (2020).

    Article 

    Google Scholar
     

  • Chun, T.-W. et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183–188 (1997).

    Article 

    Google Scholar
     

  • Maldarelli, F. et al. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science 345, 179–183 (2014).

    Article 

    Google Scholar
     

  • Douek, D. C. et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417, 95–98 (2002).

    Article 

    Google Scholar
     

  • Goulder, P. J. R. & Watkins, D. I. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat. Rev. Immunol. 8, 619–630 (2008).

    Article 

    Google Scholar
     

  • Desrosiers, R. C. Strategies used by human immunodeficiency virus that allow persistent viral replication. Nat. Med. 5, 723–725 (1999).

    Article 

    Google Scholar
     

  • Walker, B. D. & Yu, X. G. Unravelling the mechanisms of durable control of HIV-1. Nat. Rev. Immunol. 13, 487–498 (2013).

    Article 

    Google Scholar
     

  • Bailon, L. et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nat. Med. 28, 2611–2621 (2022).

    Article 

    Google Scholar
     

  • Gaiha, G. D. et al. Structural topology defines protective CD8+ T cell epitopes in the HIV proteome. Science 364, 480–484 (2019).

    Article 

    Google Scholar
     

  • Kopycinski, J. et al. Therapeutic vaccination following early antiretroviral therapy elicits highly functional T cell responses against conserved HIV-1 regions. Sci. Rep. 13, 17155 (2023).

    Article 

    Google Scholar
     

  • Lee, J. H. et al. Long-primed germinal centres with enduring affinity maturation and clonal migration. Nature 609, 998–1004 (2022).

    Article 

    Google Scholar
     

  • Wang, X. et al. mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models. Sci. Immunol. 9, eadn0622 (2024).

    Article 

    Google Scholar
     

  • Xie, Z. et al. mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. Science 384, eadk0582 (2024).

    Article 

    Google Scholar
     

  • Wood, J. M. & Robertson, J. S. From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat. Rev. Microbiol. 2, 842–847 (2004).

    Article 

    Google Scholar
     

  • Lauring, A. S., Jones, J. O. & Andino, R. Rationalizing the development of live attenuated virus vaccines. Nat. Biotechnol. 28, 573–579 (2010).

    Article 

    Google Scholar
     

  • McMichael, A. J. & Hanke, T. HIV vaccines 1983–2003. Nat. Med. 9, 874–880 (2003).

    Article 

    Google Scholar
     

  • Burton, D. R. Advancing an HIV vaccine; advancing vaccinology. Nat. Rev. Immunol. 19, 77–78 (2019).

    Article 

    Google Scholar
     

  • Haynes, B. F. et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366, 1275–1286 (2012).

    Article 

    Google Scholar
     

  • Hammer, S. M. et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N. Engl. J. Med. 369, 2083–2092 (2013).

    Article 

    Google Scholar
     

  • Gebre, M. S. et al. Novel approaches for vaccine development. Cell 184, 1589–1603 (2021).

    Article 

    Google Scholar
     

  • Travieso, T., Li, J., Mahesh, S., Mello, J. & Blasi, M. The use of viral vectors in vaccine development. npj Vaccines 7, 75 (2022).

    Article 

    Google Scholar
     

  • Picker, L. J., Lifson, J. D., Gale, M. Jr, Hansen, S. G. & Fruh, K. Programming cytomegalovirus as an HIV vaccine. Trends Immunol. 44, 287–304 (2023).

    Article 

    Google Scholar
     

  • Verweij, M. C. et al. Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy. Science 372, eabe9233 (2021).

    Article 

    Google Scholar
     

  • Borducchi, E. N. et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540, 284–287 (2016).

    Article 

    Google Scholar
     

  • Barouch, D. H. & Deeks, S. G. Immunologic strategies for HIV-1 remission and eradication. Science 345, 169–174 (2014).

    Article 

    Google Scholar
     

  • Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).

    Article 

    Google Scholar
     

  • Buchbinder, S. P. et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881–1893 (2008).

    Article 

    Google Scholar
     

  • McMichael, A. J., Borrow, P., Tomaras, G. D., Goonetilleke, N. & Haynes, B. F. The immune response during acute HIV-1 infection: clues for vaccine development. Nat. Rev. Immunol. 10, 11–23 (2010).

    Article 

    Google Scholar
     

  • Barouch, D. H. Challenges in the development of an HIV-1 vaccine. Nature 455, 613–619 (2008).

    Article 

    Google Scholar
     

  • Bournazos, S., Gazumyan, A., Seaman, M. S., Nussenzweig, M. C. & Ravetch, J. V. Bispecific anti-HIV-1 antibodies with enhanced breadth and potency. Cell 165, 1609–1620 (2016).

    Article 

    Google Scholar
     

  • Saunders, K. O. et al. Sustained delivery of a broadly neutralizing antibody in nonhuman primates confers long-term protection against simian/human immunodeficiency virus infection. J. Virol. 89, 5895–5903 (2015).

    Article 

    Google Scholar
     

  • Pegu, A. et al. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci. Transl. Med. 6, 243ra288 (2014).

    Article 

    Google Scholar
     

  • Shingai, M. et al. Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques. J. Exp. Med. 211, 2061–2074 (2014).

    Article 

    Google Scholar
     

  • Martinez-Navio, J. M. et al. Adeno-associated virus delivery of anti-HIV monoclonal antibodies can drive long-term virologic suppression. Immunity 50, 567–575.e5 (2019).

    Article 

    Google Scholar
     

  • Gardner, M. R. Promise and progress of an HIV-1 cure by adeno-associated virus vector delivery of anti-HIV-1 biologics. Front. Cell Infect. Microbiol. 10, 176 (2020).

    Article 

    Google Scholar
     

  • Priddy, F. H. et al. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial. Lancet HIV 6, e230–e239 (2019).

    Article 

    Google Scholar
     

  • Casazza, J. P. et al. Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial. Nat. Med. 28, 1022–1030 (2022).

    Article 

    Google Scholar
     

  • Nahmad, A. D. et al. In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice. Nat. Biotechnol. 40, 1241–1249 (2022).

    Article 

    Google Scholar
     

  • Liu, S. et al. Membrane-destabilizing ionizable phospholipids for organ-selective mRNA delivery and CRISPR–Cas gene editing. Nat. Mater. 20, 701–710 (2021).

    Article 

    Google Scholar
     

  • Patel, S. et al. Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA. Nat. Commun. 11, 983 (2020).

    Article 

    Google Scholar
     

  • Langer, R. & Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature 263, 797–800 (1976).

    Article 

    Google Scholar
     

  • Dimitriadis, G. J. Translation of rabbit globin mRNA introduced by liposomes into mouse lymphocytes. Nature 274, 923–924 (1978).

    Article 

    Google Scholar
     

  • Ostro, M. J., Giacomoni, D., Lavelle, D., Paxton, W. & Dray, S. Evidence for translation of rabbit globin mRNA after liposome-mediated insertion into a human cell line. Nature 274, 921–923 (1978).

    Article 

    Google Scholar
     

  • Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543, 248–251 (2017).

    Article 

    Google Scholar
     

  • Haas, J., Park, E. C. & Seed, B. Codon usage limitation in the expression of HIV-1 envelope glycoprotein. Curr. Biol. 6, 315–324 (1996).

    Article 

    Google Scholar
     

  • Kariko, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).

    Article 

    Google Scholar
     

  • Alden, M. et al. Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell line. Curr. Issues Mol. Biol. 44, 1115–1126 (2022).

    Article 

    Google Scholar
     

  • Mascola, J. R. The modern era of HIV-1 vaccine development. Science 349, 139–140 (2015).

    Article 

    Google Scholar
     

  • Parry, R., Gifford, R. J., Lytras, S., Ray, S. C. & Coin, L. J. M. No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues. Proc. Natl Acad. Sci. USA 118, e2109066118 (2021).

    Article 

    Google Scholar
     

  • Holtkamp, S. et al. Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. Blood 108, 4009–4017 (2006).

    Article 

    Google Scholar
     

  • Hassett, K. J. et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther. Nucleic Acids 15, 1–11 (2019).

    Article 

    Google Scholar
     

  • Xiao, Y. et al. Emerging mRNA technologies: delivery strategies and biomedical applications. Chem. Soc. Rev. 51, 3828–3845 (2022).

    Article 

    Google Scholar
     

  • Wolff, J. A. et al. Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468 (1990).

    Article 

    Google Scholar
     

  • Arevalo, C. P. et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 378, 899–904 (2022).

    Article 

    Google Scholar
     

  • Yaremenko, A. V., Khan, M. M., Zhen, X., Tang, Y. & Tao, W. Clinical advances of mRNA vaccines for cancer immunotherapy. Med 6, 100562 (2025).

    Article 

    Google Scholar
     

  • Pardi, N. et al. Characterization of HIV-1 nucleoside-modified mRNA vaccines in rabbits and rhesus macaques. Mol. Ther. Nucleic Acids 15, 36–47 (2019).

    Article 

    Google Scholar
     

  • Karikó, K., Muramatsu, H., Ludwig, J. & Weissman, D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 39, e142 (2011).

    Article 

    Google Scholar
     

  • Saunders, K. O. et al. Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates. npj Vaccines 6, 1–14 (2021).


    Google Scholar
     

  • Guardo, A. C. et al. Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix). AIDS 31, 321–332 (2017).

    Article 

    Google Scholar
     

  • Aldon, Y. et al. Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA. Mol. Ther. Nucleic Acids 25, 483–493 (2021).

    Article 

    Google Scholar
     

  • Bogers, W. M. et al. 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. J. Infect. Dis. 211, 947–955 (2015).

    Article 

    Google Scholar
     

  • Giraud, A. et al. Generation of monoclonal antibodies to native human immunodeficiency virus type 1 envelope glycoprotein by immunization of mice with naked RNA. J. Virol. Methods 79, 75–84 (1999).

    Article 

    Google Scholar
     

  • Weissman, D. et al. HIV Gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. J. Immunol. 165, 4710–4717 (2000).

    Article 

    Google Scholar
     

  • De Haes, W. et al. Lipoplexes carrying mRNA encoding Gag protein modulate dendritic cells to stimulate HIV-specific immune responses. Nanomedicine 8, 77–87 (2013).

    Article 

    Google Scholar
     

  • Guenaga, J. et al. mRNA lipid nanoparticles expressing cell-surface cleavage independent HIV Env trimers elicit autologous tier-2 neutralizing antibodies. Front. Immunol. 15, 1426232 (2024).

    Article 

    Google Scholar
     

  • Cu, Y. et al. Enhanced delivery and potency of self-amplifying mRNA vaccines by electroporation in situ. Vaccines 1, 367–383 (2013).

    Article 

    Google Scholar
     

  • Van Gulck, E. R. A. et al. Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins. Blood 107, 1818–1827 (2006).

    Article 

    Google Scholar
     

  • Brito, L. A. et al. A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol. Ther. 22, 2118–2129 (2014).

    Article 

    Google Scholar
     

  • Zhao, M., Li, M., Zhang, Z., Gong, T. & Sun, X. Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA. Drug Deliv. 23, 2596–2607 (2016).

    Article 

    Google Scholar
     

  • Coolen, A.-L. et al. Poly(lactic acid) nanoparticles and cell-penetrating peptide potentiate mRNA-based vaccine expression in dendritic cells triggering their activation. Biomaterials 195, 23–37 (2019).

    Article 

    Google Scholar
     

  • Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control. Rel. 217, 345–351 (2015).

    Article 

    Google Scholar
     

  • Li, M. et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways. J. Control. Rel. 228, 9–19 (2016).

    Article 

    Google Scholar
     

  • Romain, G. et al. CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional T-cell responses in nonhuman primates. Eur. J. Immunol. 42, 2019–2030 (2012).

    Article 

    Google Scholar
     

  • Allard, S. D. et al. Functional T-cell responses generated by dendritic cells expressing the early HIV-1 proteins Tat, Rev and Nef. Vaccine 26, 3735–3741 (2008).

    Article 

    Google Scholar
     

  • Van Gulck, E. et al. mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients. AIDS 26, F1–F12 (2012).

    Article 

    Google Scholar
     

  • Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).

    Article 

    Google Scholar
     

  • Xiong, S., Shah, K. & Liu, C. A zwitterionic twist. Nat. Rev. Chem. 8, 721 (2024).

    Article 

    Google Scholar
     

  • Xiao, Y. et al. High-density brush-shaped polymer lipids reduce anti-PEG antibody binding for repeated administration of mRNA therapeutics. Nat. Mater. 24, 1840–1851 (2025).

    Article 

    Google Scholar
     

  • Luozhong, S. et al. Poly(carboxybetaine) lipids enhance mRNA therapeutics efficacy and reduce their immunogenicity. Nat. Mater. 24, 1852–1861 (2025).

    Article 

    Google Scholar
     

  • Verbeke, R., Lentacker, I., De Smedt, S. C. & Dewitte, H. Three decades of messenger RNA vaccine development. Nano Today 28, 100766 (2019).

    Article 

    Google Scholar
     

  • Li, J., Xiao, C., Li, C. & He, J. Tissue-resident immune cells: from defining characteristics to roles in diseases. Signal Transduct. Target. Ther. 10, 12 (2025).

    Article 

    Google Scholar
     

  • Esteban, I. et al. In the era of mRNA vaccines, is there any hope for HIV functional cure? Viruses 13, 501 (2021).

    Article 

    Google Scholar
     

  • Lindsay, K. E. et al. Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Mol. Ther. 28, 805–819 (2020).

    Article 

    Google Scholar
     

  • Leal, L. et al. Phase I clinical trial of an intranodally administered mRNA-based therapeutic vaccine against HIV-1 infection. AIDS 32, 2533–2545 (2018).

    Article 

    Google Scholar
     

  • Gandhi, R. T. et al. Immunization of HIV-1-Infected persons with autologous dendritic cells transfected with mRNA encoding HIV-1 Gag and Nef: results of a randomized, placebo-controlled clinical trial. J. Acquir. Immune Defic. Syndr. 71, 246–253 (2016).

    Article 

    Google Scholar
     

  • Jacobson, J. M. et al. Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: a randomized, double-blind, placebo-controlled clinical trial. J. Acquir. Immune Defic. Syndr. 72, 31–38 (2016).

    Article 

    Google Scholar
     

  • Pollard, C. et al. Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. Mol. Ther. 21, 251–259 (2013).

    Article 

    Google Scholar
     

  • Diken, M. et al. Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation. Gene Ther. 18, 702–708 (2011).

    Article 

    Google Scholar
     

  • Routy, J.-P. et al. Immunologic activity and safety of autologous HIV RNA-electroporated dendritic cells in HIV-1 infected patients receiving antiretroviral therapy. Clin. Immunol. 134, 140–147 (2010).

    Article 

    Google Scholar
     

  • Gay, C. L. et al. Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection. Sci. Rep. 10, 5134 (2020).

    Article 

    Google Scholar
     

  • Allard, S. D. et al. A phase I/IIa immunotherapy trial of HIV-1-infected patients with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption. Clin. Immunol. 142, 252–268 (2012).

    Article 

    Google Scholar
     

  • de Jong, W. et al. Therapeutic vaccine in chronically HIV-1-infected patients: a randomized, double-blind, placebo-controlled phase IIa trial with HTI-TriMix. Vaccines 7, 209 (2019).

    Article 

    Google Scholar
     

  • Jong, W. D. et al. iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy. Trials 20, 361 (2019).

    Article 

    Google Scholar
     

  • Jiang, C. et al. Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature 585, 261–267 (2020).

    Article 

    Google Scholar
     

  • Collins, D. R., Gaiha, G. D. & Walker, B. D. CD8(+) T cells in HIV control, cure and prevention. Nat. Rev. Immunol. 20, 471–482 (2020).

    Article 

    Google Scholar
     

  • International HIV Controllers Study et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330, 1551–1557 (2010).

    Article 

    Google Scholar
     

  • Augusto, D. G. et al. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature 620, 128–136 (2023).

    Article 

    Google Scholar
     

  • Kaseke, C. et al. HLA class-I-peptide stability mediates CD8(+) T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV. Cell Rep. 36, 109378 (2021).

    Article 

    Google Scholar
     

  • Li, X. et al. Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide. Nat. Commun. 14, 2929 (2023).

    Article 

    Google Scholar
     

  • Chen, H. et al. TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection. Nat. Immunol. 13, 691–700 (2012).

    Article 

    Google Scholar
     

  • Bhattacharyya, S., Crain, C. R., Goldberg, B. & Gaiha, G. D. Features of functional and dysfunctional CD8+  T cells to guide HIV vaccine development. Curr. Opin. HIV AIDS 18, 257–263 (2023).

    Article 

    Google Scholar
     

  • Nathan, A. et al. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses. Cell 184, 4401–4413.e10 (2021).

    Article 

    Google Scholar
     

  • Ma, K. M. et al. HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates. Sci. Immunol. 10, eadt6660 (2025).

    Article 

    Google Scholar
     

  • Gupta, R. K. et al. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature 568, 244–248 (2019).

    Article 

    Google Scholar
     

  • Jensen, B. O. et al. In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation. Nat. Med. 29, 583–587 (2023).

    Article 

    Google Scholar
     

  • Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901–910 (2014).

    Article 

    Google Scholar
     

  • Kay, M. A. & Walker, B. D. Engineering cellular resistance to HIV. N. Engl. J. Med. 370, 968–969 (2014).

    Article 

    Google Scholar
     

  • Mock, U. et al. mRNA transfection of a novel TAL effector nuclease (TALEN) facilitates efficient knockout of HIV co-receptor CCR5. Nucleic Acids Res. 43, 5560–5571 (2015).

    Article 

    Google Scholar
     

  • Cevaal, P. M. et al. Efficient mRNA delivery to resting T cells to reverse HIV latency. Nat. Commun. 16, 4979 (2025).

    Article 

    Google Scholar
     

  • Tartof, S. Y. et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet 398, 1407–1416 (2021).

    Article 

    Google Scholar
     

  • Suthar, M. S. et al. Durability of immune responses to the BNT162b2 mRNA vaccine. Med 3, 25–27 (2022).

    Article 

    Google Scholar
     

  • Sanders, R. W. et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 9, e1003618 (2013).

    Article 

    Google Scholar
     

  • Wilhelmy, C. et al. Polysarcosine-functionalized mRNA lipid nanoparticles tailored for immunotherapy. Pharmaceutics 15, 2068 (2023).

    Article 

    Google Scholar
     

  • Doan, T. N. K., Davis, M. M. & Croyle, M. A. Identification of film-based formulations that move mRNA lipid nanoparticles out of the freezer. Mol. Ther. Nucleic Acids 35, 102179 (2024).

    Article 

    Google Scholar
     

  • Hashiba, K. et al. Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids. Commun. Biol. 7, 556 (2024).

    Article 

    Google Scholar
     

  • Kang, D. D. et al. Engineering LNPs with polysarcosine lipids for mRNA delivery. Bioact. Mater. 37, 86–93 (2024).


    Google Scholar
     

  • Bernstein, D. I. et al. Randomized, double-blind, phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers. Vaccine 28, 484–493 (2009).

    Article 

    Google Scholar
     

  • Melzi, E. et al. Membrane-bound mRNA immunogens lower the threshold to activate HIV Env V2 apex-directed broadly neutralizing B cell precursors in humanized mice. Immunity 55, 2168–2186.e6 (2022).

    Article 

    Google Scholar
     

  • Landais, E. et al. HIV envelope glycoform heterogeneity and localized diversity govern the initiation and maturation of a V2 apex broadly neutralizing antibody lineage. Immunity 47, 990–1003.e9 (2017).

    Article 

    Google Scholar
     

  • Mu, Z. et al. mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice. Cell Rep. 38, 110514 (2022).

    Article 

    Google Scholar
     

  • Ramezani-Rad, P. et al. Vaccination with an mRNA-encoded membrane-bound HIV envelope trimer induces neutralizing antibodies in animal models. Sci. Transl. Med. 17, eadw0721 (2025).

    Article 

    Google Scholar
     

  • Sanders, R. W. & Moore, J. P. Progress on priming HIV-1 immunity. Science 384, 738–739 (2024).

    Article 

    Google Scholar
     

  • Leggat, D. J. et al. Vaccination induces HIV broadly neutralizing antibody precursors in humans. Science 378, eadd6502 (2022).

    Article 

    Google Scholar
     

  • Mallapaty, S. mRNA vaccines for HIV trigger strong immune response in people. Nature 644, 311–312 (2025).

    Article 

    Google Scholar
     

  • Parayath, N. N., Stephan, S. B., Koehne, A. L., Nelson, P. S. & Stephan, M. T. In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo. Nat. Commun. 11, 6080 (2020).

    Article 

    Google Scholar
     

  • Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022).

    Article 

    Google Scholar
     

  • Anthony-Gonda, K. et al. Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Sci. Transl. Med. 11, eaav5685 (2019).

    Article 

    Google Scholar
     

  • Mangala Prasad, V. et al. Cryo-ET of Env on intact HIV virions reveals structural variation and positioning on the Gag lattice. Cell 185, 641–653.e17 (2022).

    Article 

    Google Scholar
     

  • Stewart-Jones, G. B. et al. Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G. Cell 165, 813–826 (2016).

    Article 

    Google Scholar
     

  • Haddox, H. K., Dingens, A. S. & Bloom, J. D. Experimental estimation of the effects of all amino-acid mutations to HIV’s envelope protein on viral replication in cell culture. PLoS Pathog. 12, e1006114 (2016).

    Article 

    Google Scholar
     

  • Yu, W. H. et al. Exploiting glycan topography for computational design of Env glycoprotein antigenicity. PLoS Comput. Biol. 14, e1006093 (2018).

    Article 

    Google Scholar
     

  • Zhang, H. et al. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature 621, 396–403 (2023).

    Article 

    Google Scholar
     

  • Beissert, T. et al. A trans-amplifying RNA vaccine strategy for induction of potent protective immunity. Mol. Ther. 28, 119–128 (2020).

    Article 

    Google Scholar
     

  • Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 185, 1728–1744.e16 (2022).

    Article 

    Google Scholar
     

  • Blakney, A. K., McKay, P. F., Yus, B. I., Aldon, Y. & Shattock, R. J. Inside out: optimization of lipid nanoparticle formulations for exterior complexation and in vivo delivery of saRNA. Gene Ther. 26, 363–372 (2019).

    Article 

    Google Scholar
     

  • Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109, 14604–14609 (2012).

    Article 

    Google Scholar
     

  • Melo, M. et al. Immunogenicity of RNA replicons encoding HIV Env immunogens designed for self-assembly into nanoparticles. Mol. Ther. 27, 2080–2090 (2019).

    Article 

    Google Scholar
     

  • Gay, C. L. et al. Immunogenicity of AGS-004 dendritic cell therapy in patients treated during acute HIV infection. AIDS Res. Hum. Retroviruses 34, 111–122 (2018).

    Article 

    Google Scholar
     

  • Klasse, P. J., Sanders, R. W., Ward, A. B., Wilson, I. A. & Moore, J. P. The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies. Nat. Rev. Microbiol. 23, 734–752 (2025).

    Article 

    Google Scholar
     

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