Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine<i>In Vivo</i>

Kraynyak, Kimberly A.; Kutzler, Michele A.; Cisper, Neil J.; Laddy, Dominick J.; Morrow, Matthew P.; Waldmann, Thomas A.; Weiner, David B.

doi:10.1089/hum.2009.025

Cited by 24 publications

(24 citation statements)

References 68 publications

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“…Env-EXPRESSING T LYMPHOCYTES PROTECT AGAINST FIV 3853 (2,12,34,36,57), including the cat (41), while imiquimod, which was applied at the sites of DNA injections, is a Toll-like receptor agonist known to induce the local release of several cytokines (19) as well as dendritic cell maturation and homing to draining lymph nodes (17,50). To our knowledge, these adjuvants had not been used in concert before, and the actual contribution of each of them will need to be defined in further studies.…”

Section: Vol 84 2010mentioning

confidence: 99%

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Pistello

Bonci

Zabogli

et al. 2010

J Virol

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The envelope (Env) glycoproteins of HIV and other lentiviruses possess neutralization and other protective epitopes, yet all attempts to induce protective immunity using Env as the only immunogen have either failed or afforded minimal levels of protection. In a novel prime-boost approach, specific-pathogen-free cats were primed with a plasmid expressing Env of feline immunodeficiency virus (FIV) and feline granulocyte-macrophage colony-stimulating factor and then boosted with their own T lymphocytes transduced ex vivo to produce the same Env and interleukin 15 (3 ؋ 10 6 to 10 ؋ 10 6 viable cells/cat). After the boost, the vaccinees developed elevated immune responses, including virus-neutralizing antibodies (NA). Challenge with an ex vivo preparation of FIV readily infected all eight control cats (four mock vaccinated and four naïve) and produced a marked decline in the proportion of peripheral CD4 T cells. In contrast, five of seven vaccinees showed little or no traces of infection, and the remaining two had reduced viral loads and underwent no changes in proportions of CD4 T cells. Interestingly, the viral loads of the vaccinees were inversely correlated to the titers of NA. The findings support the concept that Env is a valuable immunogen but needs to be administered in a way that permits the expression of its full protective potential.

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Section: Vol 84 2010mentioning

confidence: 99%

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Pistello

Bonci

Zabogli

et al. 2010

J Virol

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“…In a murine model administration of IL-15 enhanced the cytolytic activity of anti-HIV-specific CD8 + T cells and the production of IFN-c, [23][24][25][26] and its administration with IL-15Ra boosts these responses to even higher levels. 27 Similar effects have also been observed in rhesus macaques vaccinated against simian immunodeficiency virus (SIV) [28][29][30] or when immunized with HIV DNA vaccine. 31 The use of IL-15 as an adjuvant together with an anti-HIV vaccine is currently being tested in clinical trials (www.Clinicaltrials.gov).…”

Section: T He Main Immunological Effect Of Hiv-1 Infection Is the Promentioning

confidence: 66%

“…27 However, we cannot completely rule out that differences between studied groups in expression of icIL-15 are not the result of differential participation of the a-chain of IL-15R within the intracellular compartment. IL-15 is released only when bound to its private a-chain receptor, leaving other unbound forms behind.…”

Section: Discussionmentioning

confidence: 84%

“…17,18,38 On the basis of these findings, IL-15 can be considered to have adjuvant potential to support DNA-based anti-HIV vaccines. This cytokine enhances the cytolytic activity of anti-HIV-specific CD8 T cells and increases the production of IFNc in animal models, [23][24][25][26][27][28][29][30] and its use with anti-HIV vaccines is currently being tested in clinical trials (www.Clinicaltrials.gov). However, not all studies support the beneficial effect of IL-15.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Interleukin-15 and Interleukin-15Rα in Monocytes of HIV Type 1-Infected Patients with Different Courses of Disease Progression

Tarkowski

Ferraris²,

Martone³

et al. 2012

AIDS Research and Human Retroviruses

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Interleukin-15 (IL-15) enhances the effector mechanisms of anti-HIV immune responses and thus is considered a potential adjuvant of HIV-1 vaccine. However, there are a lack of data concerning the relationships between IL-15 expression and regulation in HIV-1-infected patients and the course of disease progression. We found that IL-15, but not IL-15Ra, is expressed at significantly higher levels in the CD14 + monocytes [stimulated or not with interferon (IFN)-c] of long-term nonprogressors (LTNP) than in those of HIV-1 progressors or healthy controls. There was no between-group difference in the amounts of soluble IL-15 released from the cells. We also found that like the healthy controls, the LTNP expressed the IL-15 and IL-15Ra genes in a more coordinated manner than the progressors. Our findings show that there are significant differences in IL-15 expression between patients with different courses of HIV infection, and that the coordinated expression of the IL-15 and IL-15Ra genes is dysregulated in patients with progressive disease. They also provide important information concerning the mechanisms of infection and the potential use of IL-15 as a therapeutic agent.

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“…Cytokines such as interleukin (IL)-12 and IL-15 have been effective in enhancing immune responses in both murine and nonhuman primate models [104,105]. This approach was used successfully against Mycobacterium tuberculosis [106], Yersinia pestis [107,108], HIV [3,109], cytomegalovirus [110], and tumors [111].…”

Section: Adjuvantsmentioning

confidence: 99%

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

Rosa¹

2015

J Vaccines Vaccin

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Vaccination has been the most efficacious way to combat infectious diseases in human history. Nevertheless, there are still a variety of pathogens for which vaccines are urgently needed. In the last 25 years, DNA vaccines emerged as promising in prophylactic and therapeutic settings. However, despite all the practical advantages, DNA vaccines face challenges in inducing potent antigen specific immune responses and protection in humans. In the last years, rational approaches to improve the efficacy of DNA vaccines were developed and include: modifications of plasmid basic design, use of next-generation delivery methods, addition of adjuvants in the formulation, improvement in immunization protocols and even targeting to dendritic cells. In this review, we will explore the advances and hurdles involved in the development of more potent DNA vaccines.

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Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA VaccineIn Vivo

Cited by 24 publications

References 68 publications

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Expression of Interleukin-15 and Interleukin-15Rα in Monocytes of HIV Type 1-Infected Patients with Different Courses of Disease Progression

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

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