Differential polarization of immune responses by genetic cotransfer of chemokines changes the protective immunity of DNA vaccine against pseudorabies virus

Yoon, Hyun Ah; Eo, Seong Kug

doi:10.1111/j.1365-2567.2006.02490.x

Cited by 19 publications

(15 citation statements)

References 43 publications

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“…Furthermore, our results would indicate that statins could be utilized as immunomodulatory agents with the capacity to alter induced immune responses. It has been shown that the Th-1 and Th-2 cytokine secretory balance can be altered by statin treatment with the net effect of modulating induced immune responses against viral antigens [15], [22]–[24]. This could have implications for modulating the type of cellular immune response mounted in HIV-1 infected patients, with a preferential skewing towards a strengthened Th1 response and heightened CTL activity.…”

Section: Resultsmentioning

confidence: 99%

Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

et al. 2007

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BackgroundStatins have previously been shown to reduce the in vitro infection of human immunodeficiency virus type 1 (HIV-1) through modulation of Rho GTPase activity and lipid raft formation at the cell surface, as well as by disrupting LFA-1 incorporation into viral particles.Principle FindingsHere we demonstrate that treatment of an enriched CD4+ lymphocyte population with lovastatin (Lov), mevastatin (Mev) and simvastatin (activated and non-activated, Sim(A) and Sim(N), respectively) can reduce the cell surface expression of the CC-chemokine receptor CCR5 (P<0.01 for Sim(A) and Lov). The lowered CCR5 expression was associated with down-regulation of CCR5 mRNA expression. The CC-chemokine RANTES protein and mRNA expression levels were slightly increased in CD4+ enriched lymphocytes treated with statins. Both R5 and X4 HIV-1 were reduced for their infection of statin-treated cells; however, in cultures where statins were removed and where a decrease in CCR5 expression was observed, there was a preferential inhibition of infection with an R5 versus X4 virus.ConclusionsThe results indicate that the modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression levels should be considered as contributing to the anti-viral effects of statins, preferentially inhibiting R5 viruses. This observation, in combination with the immunomodulatory activity exerted by statins, suggests they may possess more potent anti-HIV-1 activity when applied during the early stages of infection or in lowering viral transmission. Alternatively, statin treatment could be considered as a way to modulate immune induction such as during vaccination protocols.

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Section: Resultsmentioning

confidence: 99%

Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

et al. 2007

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“…Other studies reported on the use of chemokines for the modulation of immune responses against viral antigens, where it was demonstrated that the coexpression of CCL3 from a DNA vaccine resulted in improved cellular and humoral immune responses against HIV proteins, with a predominant Th1 immunity (26). Interestingly, another report that compared different chemokines as genetic adjuvants for DNA-based immunization against pseudorabies virus showed a bias to Th2 after codelivery of CCL3 (47), suggesting that the predominance of either Th1 or Th2 is not strictly determined by the codelivered chemokine. One publication reports on the coexpression of CCL20 from a modified vaccinia virus Ankara-based vector and shows enhanced cellular and binding antibody responses compared to vaccination with antigen alone, which is in accordance with our results, but no data on vaccine protection after a challenge infection were shown (5).…”

Section: Discussionmentioning

confidence: 99%

“…A different approach is the coexpression of chemoattractant molecules by a genetic vaccine to recruit APCs to the site of vaccine delivery. This approach has been studied in immunotherapy of tumors (16,19,34,46) and also for vaccination against virus infections (5,13,26,47), but it has not yet been tested in a retrovirus challenge model.…”

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confidence: 99%

Codelivery of the Chemokine CCL3 by an Adenovirus-Based Vaccine Improves Protection from Retrovirus Infection

Lietz

Bayer

Ontikatze

et al. 2012

J Virol

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. After antigen uptake and activation, DCs mature and migrate to lymphoid tissues, where they present antigen-derived peptides on major histocompatibility complex type II (MHC-II) molecules and provide stimulatory signals for antigen-specific T cells. Because of the important role of DCs in the induction of protective immunity, DC targeting of antigens has been a much-pursued strategy in the development of genetic and protein-based vaccines. For this, vaccine antigens were fused to antibodies or ligands of DC surface molecules and delivered directly as a protein vaccine or through encoding DNA in a genetic plasmid-or viral vectorbased vaccine regimen (4,33,37,43,44). A different approach is the coexpression of chemoattractant molecules by a genetic vaccine to recruit APCs to the site of vaccine delivery. This approach has been studied in immunotherapy of tumors (16,19,34,46) and also for vaccination against virus infections (5, 13, 26, 47), but it has not yet been tested in a retrovirus challenge model.In this vaccination study we sought to increase the presence of DCs at the site of vaccine delivery. For this, we coadministered adenovirus vectors encoding different chemokines along with viral antigens. Chemokines are a group of proinflammatory proteins of 6 to 14 kDa that act as ligands of G-protein-coupled receptors (reviewed in reference 31) expressed on leukocytes. Chemokines induce the migration of these cells and play an important role in both homeostasis and inflammation. For these different processes, some chemokines are expressed continuously in certain tissues, while others are only expressed in response to inflammatory stimuli. Depending on the expression of their respective receptors, chemokines can stimulate multiple cell types. In the present study we studied the effects of the chemokines CCL3, CCL20, CCL21, and CXCL14 on immune responses induced by an adenovirus-based vaccine. All four tested chemokines, while acting on differing ranges of target cells, are known to be chemoattractants for DCs (reviewed in reference 48).We analyzed the adjuvant effect of chemokines for retroviral immunity using an HIV vaccination mouse model and the Friend retrovirus (FV) model. FV is an immunosuppressive retroviral complex, consisting of the apathogenic Friend murine leukemia virus (F-MuLV) and the replication-defective but pathogenic spleen focus-forming virus, that causes splenomegaly and lethal erythroleukemia in susceptible mice (15). In contrast to the vaccination against HIV proteins, the FV model allows for challenging immunized mice with a pathogenic retrovirus. The FV infection model has offered valuable insights into the role of particular cell types in the immune response to a retroviral infection and into the basic requirements for immune protection. Using attenuated F-MuLV helper virus, it was demonstrated that complete protection from lethal FV challenge requires both humoral and cellular responses, comprising antibodies and CD4 ϩ and CD8 ϩ T cells (10). Although the correlates of immune protection ...

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“…Briefly, ELISA plates were coated overnight at 4°C with an optimal dilution (0.5–1.0 μg/well) of the semi‐purified PrV antigen for sample wells and with goat anti‐swine IgG for standard wells (Bethyl Laboratories, Montgomery, TX, USA). The viral antigen used for the coating was prepared by treating the viral stock with 0.5% Triton X‐100 and then semi‐purified by centrifugation at 50 000 g (23). The plates were then washed three times with PBS‐Tween 20 (PBST), after which they were blocked with 3% nonfat‐dried milk.…”

Section: Methodsmentioning

confidence: 99%

Co‐administration of live attenuated Salmonella enterica serovar Typhimurium expressing swine interleukin‐18 and interferon‐α provides enhanced Th1‐biased protective immunity against inactivated vaccine of pseudorabies virus

Kim

Han

et al. 2012

Microbiology and Immunology

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The co-administration of two or more cytokines may generate additive or synergistic effects for controlling infectious diseases. However, the practical use of cytokine combinations for the modulation of immune responses against inactivated vaccine has not been demonstrated in livestock yet, primarily due to protein stability, production, and costs associated with mass administration. In light of the current situation, we evaluated the immunomodulatory functions of the combined administration of swine interleukin-18 (swIL-18) and interferon-α (swIFN-α) against an inactivated PrV vaccine using attenuated Salmonella enterica serovar Typhimurium as a cytokine delivery system. Co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α produced enhanced Th1-biased humoral and cellular immune responses against the inactivated PrV vaccine, when compared to single administration of S. enterica serovar Typhimurium expressing either swIL-18 or swIFN-α. Also, enhanced immune responses in co-administered piglets occurred rapidly after virulent PrV challenge, and piglets that received coadministration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α displayed a greater alleviation of clinical severity following the virulent PrV challenge, as determined by clinical scores and cumulative daily weight gain. Furthermore, this enhancement was confirmed by reduced nasal shedding of PrV following viral challenge. Therefore, these results suggest that oral co-administration of S. enterica serovar Typhimurium expressing swIL-18 and swIFN-α provide enhanced Th1-biased immunity against inactivated PrV vaccine to alleviate clinical signs caused by PrV challenge.

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Differential polarization of immune responses by genetic cotransfer of chemokines changes the protective immunity of DNA vaccine against pseudorabies virus

Cited by 19 publications

References 43 publications

Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

Statins Disrupt CCR5 and RANTES Expression Levels in CD4+ T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

Codelivery of the Chemokine CCL3 by an Adenovirus-Based Vaccine Improves Protection from Retrovirus Infection

Co‐administration of live attenuated Salmonella enterica serovar Typhimurium expressing swine interleukin‐18 and interferon‐α provides enhanced Th1‐biased protective immunity against inactivated vaccine of pseudorabies virus

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