Enhancement of HIV-1 env-specific CD8 T cell responses using interferon-stimulated gene 15 as an immune adjuvant
Entity
UAM. Departamento de Medicina Preventiva y Salud Pública y MicrobiologíaPublisher
American Society for MicrobiologyDate
2020-12-22Citation
10.1128/JVI.01155-20
Journal of Virology 95.2 (2022): 1-16
ISSN
0022-538X (print); 1098-5514 (online)DOI
10.1128/JVI.01155-20Funded by
This project was supported by the Spanish Ministerio de Economía, Industria y Competitividad and FEDER/FSE (SAF2017-88089-R to S.G. and M.E.). Michela Falquireceived a Formación de Personal Investigador Ph.D. fellowship from the Spanish Ministry of Health and EducationProject
Gobierno de España. SAF2017-88089-REditor's Version
https://doi.org/10.1128/jvi.01155-20Subjects
alarmin; DNA vectors; HIV vaccine; immune responses; ISG15; ISG15 adjuvant; MVA-B; vaccines; MedicinaRights
© 2020 American Society for MicrobiologyAbstract
Induction of the endogenous innate immune system by interferon (IFN) triggers the expression of many proteins that serve like alarm bells in the body, activating an immune response. After a viral infection, one of the genes activated by IFN induction is the IFN-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein that undergoes a reversible posttranslational modification (ISGylation). ISG15 protein can also act unconjugated, intracellularly and secreted, acting as a cytokine. Although ISG15 has an essential role in host defense responses to microbial infection, its role as an immunomodulator in the vaccine field remains to be defined. In this investigation, we showed that ISG15 exerts an immunomodulatory role in human immunodeficiency virus (HIV) vaccines. In mice, after priming with a DNA-ISG15 vector mixed with a DNA expressing HIV-1 gp120 (DNA-gp120), followed by a booster with a modified vaccinia virus Ankara (MVA) vector expressing HIV-1 antigens, both wild-type ISG15-conjugated (ISG15-wt) and mutant unconjugated (ISG15-mut) proteins act as immune adjuvants by increasing the magnitude and quality of HIV-1-specific CD8 T cells, with ISG15-wt providing better immunostimulatory activity than ISG15-mut. The HIV-1 Env-specific CD8 T cell responses showed a predominant T effector memory (TEM) phenotype in all groups. Moreover, the amount of DNAgp120 used to immunize mice could be reduced 5-fold after mixing with DNA-ISG15 without affecting the potency and the quality of the HIV-1 Env-specific immune responses. Our study clearly highlights the potential use of the IFN-induced ISG15 protein as immune adjuvant to enhance immune responses to HIV antigens, suggesting that this molecule might be exploitable for prophylactic and therapeutic vaccine approaches against pathogens. IMPORTANCE Our study described the potential role of ISG15 as an immunomodulatory molecule in the optimization of HIV/AIDS vaccine candidates. Using a DNA prime–MVA boost immunization protocol, our results indicated an increase in the potency and the quality of the HIV-1 Env-specific CD8 T cell response. These results highlight the adjuvant potency of ISG15 to elicit improved viral antigen presentation to the immune system, resulting in an enhanced HIV-1 vaccine immune response. The DNA-ISG15 vector could find applicability in the vaccine field in combination with other nucleic acid-based vector vaccines
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Google Scholar:Gómez, Carmen Elena
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Perdiguero, Beatriz
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Falqui, Michela Maria Eugenia
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Marín, María Q.
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Bécares Palacios, Martina
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Sorzano, Carlos Oscar S.
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García Arriaza, Juan Francisco
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Esteban, Mariano
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Guerra García, María Susana
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