a3af10d65de0386b0579062c6ee5953c 301973.pdf 9cb6da91f1a68f7bcb2d30c5e531fd7589552624 301973.pdf 7a3f527f9f7889b1f346c6276a11df8dffe4f9b2b7fab65f708fa19445218d5b 301973.pdf Title: Nucleic Acid Vaccines Encoding Proteins and Virus-like Particles for HIV Prevention Subject: The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4+ and CD8+ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV. Keywords: AIDS; mRNA; DNA; VLP; antibody; bNAbs; Env; Gag Author: Ferran Tarrés-Freixas, Bonaventura Clotet, Jorge Carrillo and Julià Blanco Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Mar 13 07:06:06 2024 CET ModDate: Wed Mar 13 07:11:31 2024 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 23 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1705237 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWJZGO+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 HFZUYQ+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 HXFOSU+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 TZYXLI+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 JQEESF+VnURWPalladioL Type 1 Custom yes yes yes 32 0 JGODGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 72 0 JGODGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 75 0 JGODGN+PalatinoLinotype TrueType WinAnsi yes yes no 81 0 JGODHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 84 0 JGODON+PalatinoLinotype TrueType MacRoman yes yes no 87 0 JGODGK+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 101 0 JGODGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 107 0 JGODGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 110 0 JGODGN+PalatinoLinotype TrueType WinAnsi yes yes no 116 0 JGODHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 119 0 JGODON+PalatinoLinotype TrueType MacRoman yes yes no 122 0 JGODGL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 145 0 JGODGM+PalatinoLinotype CID TrueType Identity-H yes yes yes 148 0 JGODGN+PalatinoLinotype TrueType WinAnsi yes yes no 154 0 JGODHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 157 0 JGODON+PalatinoLinotype TrueType MacRoman yes yes no 160 0 QGUKZH+CMSY10 Type 1 Builtin yes yes yes 167 0 MKDWFJ+EURM10 Type 1 Builtin yes yes yes 213 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-07 02:44:27 CET RepresentationInformation: 301973.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-06 13:01:32 CET Size: 1705237 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 717 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Which Immunogens Should We Use and Why? Destination: section.2 Children: Item: Title: Elicitation of Protective Humoral Responses Destination: subsection.2.1 Item: Title: Elicitation of Protective T Cell Responses Destination: subsection.2.2 Item: Title: HIV Vaccine Efficacy Trials: Past Failures, Future Successes Destination: section.3 Item: Title: Nucleic Acid Vaccines and Their Delivery Destination: section.4 Children: Item: Title: Viral Vectored HIV Vaccines Destination: subsection.4.1 Item: Title: DNA and mRNA HIV Vaccines Destination: subsection.4.2 Children: Item: Title: Nucleic Acid Vaccines Encoding Viral Particles Destination: subsubsection.4.2.1 Item: Title: Nucleic Acid Vaccines Encoding Virus-like Particles Destination: subsubsection.4.2.2 Item: Title: Summary and Future Directions Destination: subsection.4.3 Item: Title: References Destination: section.5 Info: Title: Nucleic Acid Vaccines Encoding Proteins and Virus-like Particles for HIV Prevention Author: Ferran Tarrés-Freixas, Bonaventura Clotet, Jorge Carrillo and Julià Blanco Subject: The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4+ and CD8+ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV. 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