Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
Development of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/9/959 |
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| author | Carmen Elena Gómez Beatriz Perdiguero Lorena Usero Laura Marcos-Villar Laia Miralles Lorna Leal Carlos Óscar S. Sorzano Cristina Sánchez-Corzo Montserrat Plana Felipe García Mariano Esteban |
| author_facet | Carmen Elena Gómez Beatriz Perdiguero Lorena Usero Laura Marcos-Villar Laia Miralles Lorna Leal Carlos Óscar S. Sorzano Cristina Sánchez-Corzo Montserrat Plana Felipe García Mariano Esteban |
| author_sort | Carmen Elena Gómez |
| collection | DOAJ |
| description | Development of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based on unmodified vectors and the other on 1-methyl-3′-pseudouridylyl modified vectors expressing a T cell multiepitopic construct including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (referred to as RNA-TMEP and RNA-TMEPmod, respectively) and defined their biological and immunological properties in cultured cells and in mice. In cultured cells, both mRNA vectors expressed the corresponding protein, with higher levels observed in the unmodified mRNA, leading to activated macrophages with differential induction of innate immune molecules. In mice, intranodal administration of the mRNAs induced the activation of specific T cell (CD4 and CD8) responses, and the levels were markedly enhanced after a booster immunization with the poxvirus vector MVA-TMEP expressing the same antigen. This immune activation was maintained even three months later. These findings revealed a potent combined immunization regimen able to enhance the HIV-1-specific immune responses induced by an mRNA vaccine that might be applicable to human vaccination programs with mRNA and MVA vectors. |
| first_indexed | 2024-03-10T07:09:32Z |
| format | Article |
| id | doaj.art-539a6a02a59d4afbabaf298b8e811bd1 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T07:09:32Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-539a6a02a59d4afbabaf298b8e811bd12023-11-22T15:34:03ZengMDPI AGVaccines2076-393X2021-08-019995910.3390/vaccines9090959Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same AntigenCarmen Elena Gómez0Beatriz Perdiguero1Lorena Usero2Laura Marcos-Villar3Laia Miralles4Lorna Leal5Carlos Óscar S. Sorzano6Cristina Sánchez-Corzo7Montserrat Plana8Felipe García9Mariano Esteban10Centro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainCentro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainAIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, SpainCentro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainAIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, SpainAIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, SpainBiocomputing Unit and Computational Genomics, CNB-CSIC, 28049 Madrid, SpainCentro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainAIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, SpainAIDS Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, 08036 Barcelona, SpainCentro Nacional de Biotecnología (CNB), Department of Molecular and Cellular Biology, Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, SpainDevelopment of a vaccine against HIV remains a major target goal in the field. The recent success of mRNA vaccines against the coronavirus SARS-CoV-2 is pointing out a new era of vaccine designs against pathogens. Here, we have generated two types of mRNA vaccine candidates against HIV-1; one based on unmodified vectors and the other on 1-methyl-3′-pseudouridylyl modified vectors expressing a T cell multiepitopic construct including protective conserved epitopes from HIV-1 Gag, Pol and Nef proteins (referred to as RNA-TMEP and RNA-TMEPmod, respectively) and defined their biological and immunological properties in cultured cells and in mice. In cultured cells, both mRNA vectors expressed the corresponding protein, with higher levels observed in the unmodified mRNA, leading to activated macrophages with differential induction of innate immune molecules. In mice, intranodal administration of the mRNAs induced the activation of specific T cell (CD4 and CD8) responses, and the levels were markedly enhanced after a booster immunization with the poxvirus vector MVA-TMEP expressing the same antigen. This immune activation was maintained even three months later. These findings revealed a potent combined immunization regimen able to enhance the HIV-1-specific immune responses induced by an mRNA vaccine that might be applicable to human vaccination programs with mRNA and MVA vectors.https://www.mdpi.com/2076-393X/9/9/959HIV-1 mRNA vaccinesmultiepitopic proteinintranodal deliveryT cellspoxvirus MVA vectormice |
| spellingShingle | Carmen Elena Gómez Beatriz Perdiguero Lorena Usero Laura Marcos-Villar Laia Miralles Lorna Leal Carlos Óscar S. Sorzano Cristina Sánchez-Corzo Montserrat Plana Felipe García Mariano Esteban Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen Vaccines HIV-1 mRNA vaccines multiepitopic protein intranodal delivery T cells poxvirus MVA vector mice |
| title | Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen |
| title_full | Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen |
| title_fullStr | Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen |
| title_full_unstemmed | Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen |
| title_short | Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen |
| title_sort | enhancement of the hiv 1 specific immune response induced by an mrna vaccine through boosting with a poxvirus mva vector expressing the same antigen |
| topic | HIV-1 mRNA vaccines multiepitopic protein intranodal delivery T cells poxvirus MVA vector mice |
| url | https://www.mdpi.com/2076-393X/9/9/959 |
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