1. Enhancement of the HIV-1-Specific Immune Response Induced by an mRNA Vaccine through Boosting with a Poxvirus MVA Vector Expressing the Same Antigen
- Author
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Lorena Usero, Carlos Oscar S. Sorzano, Cristina Sánchez-Corzo, Montserrat Plana, Mariano Esteban, Felipe García, Laura Marcos-Villar, Laia Miralles, Beatriz Perdiguero, Lorna Leal, Carmen E. Gómez, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Instituto de Salud Carlos III, Generalitat de Catalunya, Gómez, Carmen E., Leal, Lorna, Sorzano, Carlos Óscar S., García, Felipe, Esteban, Mariano, Gómez, Carmen E. [0000-0002-5414-7935], Leal, Lorna [0000-0001-7887-6027], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], García, Felipe [0000-0001-7658-5832], and Esteban, Mariano [0000-0003-0846-2827]
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mice ,T cell ,viruses ,Intranodal delivery ,Immunology ,T cells ,Immune responses ,Biology ,Combined vaccines ,Epitope ,Article ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,intranodal delivery ,Antigen ,Drug Discovery ,HIV-1 mRNA vaccines ,medicine ,Pharmacology (medical) ,Vector (molecular biology) ,Poxvirus MVA vector ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Innate immune system ,prime/boost ,virus diseases ,multiepitopic protein ,Multiepitopic protein ,combined vaccines ,Acquired immune system ,Virology ,immune responses ,3. Good health ,poxvirus MVA vector ,Vaccination ,Infectious Diseases ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Medicine ,Prime/boost - Abstract
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., This study was partially supported by grants from the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, SAF-2017-88089-R, RTI2018-096309-B-I00); the Fondo Europeo para el Desarrollo Regional (FEDER); the SPANISH AIDS Research Network RD16/0025/0002 and RD16/0025/0014-ISCIII-FEDER (RIS); the Fondo de Investigación Sanitaria (FIS) AC16/00051 and PI18/00699; the Instituto de Salud Carlos III (grants: COV20/00214; ICI20/00067) and the CERCA Programme/Generalitat de Catalunya SGR 615 and SGR 653. This manuscript was funded by the European Commission [grant numbers: FP7-HEALTH-2013-INNOVATION-1 602570-2, H2020-SC1- 2016-2017 (H2020-SC1-2016-RTD) Proposal: 731626-HIVACAR].
- Published
- 2021
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