HIV MRNA Vaccines-Progress and Future Paths

Overview

Journal Vaccines (Basel)

Date 2021 Feb 10

PMID 33562203

Citations 38

Authors

Zekun Mu

Barton F Haynes

Derek W Cain

Affiliations

Soon will be listed here.

Abstract

The SARS-CoV-2 pandemic introduced the world to a new type of vaccine based on mRNA encapsulated in lipid nanoparticles (LNPs). Instead of delivering antigenic proteins directly, an mRNA-based vaccine relies on the host's cells to manufacture protein immunogens which, in turn, are targets for antibody and cytotoxic T cell responses. mRNA-based vaccines have been the subject of research for over three decades as a platform to protect against or treat a variety of cancers, amyloidosis and infectious diseases. In this review, we discuss mRNA-based approaches for the generation of prophylactic and therapeutic vaccines to HIV. We examine the special immunological hurdles for a vaccine to elicit broadly neutralizing antibodies and effective T cell responses to HIV. Lastly, we outline an mRNA-based HIV vaccination strategy based on the immunobiology of broadly neutralizing antibody development.

Citing Articles

Functionality and translation fidelity characterization of mRNA vaccines using platform based mass spectrometry detection.

Stiving A, Roose B, Tubbs C, Haverick M, Gruber A, Rustandi R NPJ Vaccines. 2025; 10(1):38.

PMID: 39988579 PMC: 11847942. DOI: 10.1038/s41541-025-01082-4.

Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications.

Shi Y, Shi M, Wang Y, You J Signal Transduct Target Ther. 2024; 9(1):322.

PMID: 39543114 PMC: 11564800. DOI: 10.1038/s41392-024-02002-z.

Identification of antibody targets associated with lower HIV viral load and viremic control.

Grant-McAuley W, Morgenlander W, Ruczinski I, Kammers K, Laeyendecker O, Hudelson S PLoS One. 2024; 19(9):e0305976.

PMID: 39288118 PMC: 11407625. DOI: 10.1371/journal.pone.0305976.

mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends.

Gao Y, Yang L, Li Z, Peng X, Li H Biomark Res. 2024; 12(1):93.

PMID: 39217377 PMC: 11366172. DOI: 10.1186/s40364-024-00644-3.

Messenger RNA Vaccine Technology: Success for SARS-CoV-2 and Prospects for an HIV-1 Vaccine.

Files J, Goepfert P Top Antivir Med. 2024; 32(2):420-430.

PMID: 39141920 PMC: 11293605.

References

Eisen H, Siskind G . VARIATIONS IN AFFINITIES OF ANTIBODIES DURING THE IMMUNE RESPONSE. Biochemistry. 1964; 3:996-1008. DOI: 10.1021/bi00895a027. View

Tuosto L, Acuto O . CD28 affects the earliest signaling events generated by TCR engagement. Eur J Immunol. 1998; 28(7):2131-42. DOI: 10.1002/(SICI)1521-4141(199807)28:07<2131::AID-IMMU2131>3.0.CO;2-Q. View

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. 2005; 23(2):165-75. DOI: 10.1016/j.immuni.2005.06.008. View

Jardine J, Kulp D, Havenar-Daughton C, Sarkar A, Briney B, Sok D . HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science. 2016; 351(6280):1458-63. PMC: 4872700. DOI: 10.1126/science.aad9195. View

Barre-Sinoussi F, Ross A, Delfraissy J . Past, present and future: 30 years of HIV research. Nat Rev Microbiol. 2013; 11(12):877-83. DOI: 10.1038/nrmicro3132. View

Tyler B, Gullotti D, Mangraviti A, Utsuki T, Brem H . Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv Drug Deliv Rev. 2016; 107:163-175. DOI: 10.1016/j.addr.2016.06.018. View

Pallesen J, Wang N, Corbett K, Wrapp D, Kirchdoerfer R, Turner H . Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc Natl Acad Sci U S A. 2017; 114(35):E7348-E7357. PMC: 5584442. DOI: 10.1073/pnas.1707304114. View

Theiler J, Yoon H, Yusim K, Picker L, Fruh K, Korber B . Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci Rep. 2016; 6:33987. PMC: 5050445. DOI: 10.1038/srep33987. View

Verkoczy L, Chen Y, Bouton-Verville H, Zhang J, Diaz M, Hutchinson J . Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls. J Immunol. 2011; 187(7):3785-97. PMC: 3192533. DOI: 10.4049/jimmunol.1101633. View

10.

Saeboe-Larssen S, Fossberg E, Gaudernack G . mRNA-based electrotransfection of human dendritic cells and induction of cytotoxic T lymphocyte responses against the telomerase catalytic subunit (hTERT). J Immunol Methods. 2001; 259(1-2):191-203. DOI: 10.1016/s0022-1759(01)00506-3. View

11.

Kariko K, Muramatsu H, Welsh F, Ludwig J, Kato H, Akira S . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008; 16(11):1833-40. PMC: 2775451. DOI: 10.1038/mt.2008.200. View

12.

Kariko K, Muramatsu H, Keller J, Weissman D . Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin. Mol Ther. 2012; 20(5):948-53. PMC: 3345990. DOI: 10.1038/mt.2012.7. View

13.

Sok D, Le K, Vadnais M, Saye-Francisco K, Jardine J, Torres J . Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows. Nature. 2017; 548(7665):108-111. PMC: 5812458. DOI: 10.1038/nature23301. View

14.

Fruh K, Picker L . CD8+ T cell programming by cytomegalovirus vectors: applications in prophylactic and therapeutic vaccination. Curr Opin Immunol. 2017; 47:52-56. PMC: 5626601. DOI: 10.1016/j.coi.2017.06.010. View

15.

Medina-Ramirez M, Garces F, Escolano A, Skog P, de Taeye S, Moral-Sanchez I . Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo. J Exp Med. 2017; 214(9):2573-2590. PMC: 5584115. DOI: 10.1084/jem.20161160. View

16.

Corbett K, Flynn B, Foulds K, Francica J, Boyoglu-Barnum S, Werner A . Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N Engl J Med. 2020; 383(16):1544-1555. PMC: 7449230. DOI: 10.1056/NEJMoa2024671. View

17.

Bloom K, van den Berg F, Arbuthnot P . Self-amplifying RNA vaccines for infectious diseases. Gene Ther. 2020; 28(3-4):117-129. PMC: 7580817. DOI: 10.1038/s41434-020-00204-y. View

18.

Zeng Q, Jiang H, Wang T, Zhang Z, Gong T, Sun X . Cationic micelle delivery of Trp2 peptide for efficient lymphatic draining and enhanced cytotoxic T-lymphocyte responses. J Control Release. 2014; 200:1-12. DOI: 10.1016/j.jconrel.2014.12.024. View

19.

Jardine J, Julien J, Menis S, Ota T, Kalyuzhniy O, McGuire A . Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013; 340(6133):711-6. PMC: 3689846. DOI: 10.1126/science.1234150. View

20.

Geall A, Verma A, Otten G, Shaw C, Hekele A, Banerjee K . Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci U S A. 2012; 109(36):14604-9. PMC: 3437863. DOI: 10.1073/pnas.1209367109. View