Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice

Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic. Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env–gag virus-like particles (VLPs) were generated through co-tran...

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Main Authors: Qi Ma, Jing Yang, Xiaoguang Zhang, Hongxia Li, Yanzhe Hao, Xia Feng
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/1/84
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author Qi Ma
Jing Yang
Xiaoguang Zhang
Hongxia Li
Yanzhe Hao
Xia Feng
author_facet Qi Ma
Jing Yang
Xiaoguang Zhang
Hongxia Li
Yanzhe Hao
Xia Feng
author_sort Qi Ma
collection DOAJ
description Background: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic. Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env–gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines. BALB/c mice were immunized with env mRNA, env–gag VLP mRNA, env plasmid DNA vaccine, or lipid nanoparticle (LNP) controls. HIV Env-specific binding and neutralizing antibodies in mouse sera were assessed via enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays, respectively. Env-specific cellular immune responses in mouse splenocytes were evaluated using an Enzyme-linked immunosorbent assay (ELISpot) and in vivo cytotoxic T cell-killing assays. Results: The Env-specific humoral and cellular immune responses elicited by HIV-1 env mRNA and env–gag VLP mRNA vaccine were stronger than those induced by the DNA vaccine. Specific immune responses induced by the env mRNA vaccine were significantly stronger in the high-dose group than in the low-dose group. Immunization with co-formulated env and gag mRNAs elicited superior cellular immune responses compared to env mRNA alone. Conclusions: These findings suggest that the env–gag VLP mRNA platform holds significant promise for HIV-1 vaccine development.
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spelling doaj-art-dd88570681c64913a8385ccfa864475f2025-01-24T13:51:53ZengMDPI AGVaccines2076-393X2025-01-011318410.3390/vaccines13010084Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in MiceQi Ma0Jing Yang1Xiaoguang Zhang2Hongxia Li3Yanzhe Hao4Xia Feng5National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, ChinaBackground: The development of a protective vaccine is critical for conclusively ending the human immunodeficiency virus (HIV) epidemic. Methods: We constructed nucleotide-modified mRNA vaccines expressing HIV-1 Env and Gag proteins. Env–gag virus-like particles (VLPs) were generated through co-transfection with env and gag mRNA vaccines. BALB/c mice were immunized with env mRNA, env–gag VLP mRNA, env plasmid DNA vaccine, or lipid nanoparticle (LNP) controls. HIV Env-specific binding and neutralizing antibodies in mouse sera were assessed via enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays, respectively. Env-specific cellular immune responses in mouse splenocytes were evaluated using an Enzyme-linked immunosorbent assay (ELISpot) and in vivo cytotoxic T cell-killing assays. Results: The Env-specific humoral and cellular immune responses elicited by HIV-1 env mRNA and env–gag VLP mRNA vaccine were stronger than those induced by the DNA vaccine. Specific immune responses induced by the env mRNA vaccine were significantly stronger in the high-dose group than in the low-dose group. Immunization with co-formulated env and gag mRNAs elicited superior cellular immune responses compared to env mRNA alone. Conclusions: These findings suggest that the env–gag VLP mRNA platform holds significant promise for HIV-1 vaccine development.https://www.mdpi.com/2076-393X/13/1/84HIV-1 vaccinemRNA vaccineVLP vaccine
spellingShingle Qi Ma
Jing Yang
Xiaoguang Zhang
Hongxia Li
Yanzhe Hao
Xia Feng
Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
Vaccines
HIV-1 vaccine
mRNA vaccine
VLP vaccine
title Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
title_full Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
title_fullStr Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
title_full_unstemmed Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
title_short Immunogenicity of HIV-1 <i>Env</i> mRNA and <i>Env-Gag</i> VLP mRNA Vaccines in Mice
title_sort immunogenicity of hiv 1 i env i mrna and i env gag i vlp mrna vaccines in mice
topic HIV-1 vaccine
mRNA vaccine
VLP vaccine
url https://www.mdpi.com/2076-393X/13/1/84
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