Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques

Meide, P. H. Van Der; Villinger, François; Ansari, Aftab A.; Groenestein, Reno J.; Labie, M. C. D. C. De; Hout, Yvon J.M. van den; Koornstra, Wim; Bogers, Willy; Heeney, Jonathan L.

doi:10.1016/s0264-410x(02)00101-9

Cited by 16 publications

(7 citation statements)

References 26 publications

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“…Identifying adjuvants that induce DCs to secrete IL-12 might improve vaccines aiming at efficient induction of neutralizing antibodies. Indeed, studies with rhesus macaques have concluded that IL-12 enhances the induction of specific antibody responses in vivo when used as vaccine adjuvant, (Hirao et al, 2008; Schadeck et al, 2006; van der Meide et al, 2002). In contrast, blocking of IL-12 might be beneficial to prevent the development of autoreactive B cells in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

et al. 2009

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Summary T follicular helper (Tfh) cells help development of antibody responses via Interleukin-21 (IL-21). Here we show that activated human dendritic cells (DCs) induced naïve CD4+ T cells to become IL-21-producing Tfh-like cells through IL-12. CD4+ T cells primed with IL-12 induced B cells to produce immunoglobulins in a fashion dependent on IL-21 and inducible costimulator (ICOS), thus sharing fundamental characteristics with Tfh cells. The induction of Tfh-like cells by activated DCs was inhibited by neutralizing IL-12. IL-12 induced two different IL-21-producers: IL-21+IFN-γ+T-bet+ Th1 cells and IL-21+IFN-γ-T-bet- non-Th1 cells, in a manner dependent on signal transducer and activator of transcription (STAT)4. IL-12 also regulated IL-21 secretion by memory CD4+ T cells. Thus, IL-12 produced by activated DCs regulates antibody responses via developing IL-21-producing Tfh-like cells, and inducing IL-21 secretion from memory CD4+ T cells. These data suggest that the developmental pathway of Tfh cells differs between mice and humans, which have considerable implications for vaccine development.

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Section: Discussionmentioning

confidence: 99%

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

et al. 2009

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“…IL-12 acts as adjuvant for both CD4 and CD8 T-cell responses. When administered as a DNA expression vector in combination with other DNA vaccines, it increased cellular immunity in mice (24) and enhanced both humoral and cellular immune responses in rhesus macaques (11,13,57,61). Recently, the addition of IL-12 DNA plasmids to a SIVgag DNA vaccine regimen and to a prime/ boost DNA/vesicular stomatitis virus-SIVgag regimen increased protective efficacy against a SHIV 89.6P challenge (11,13).…”

mentioning

confidence: 99%

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Demberg

Boyer

Malkevich

et al. 2008

J Virol

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AIDS is one of the greatest pandemics of our time, affecting the health and the social and economic foundations of countries worldwide. A potent human immunodeficiency virus (HIV) vaccine offers the best hope for controlling the spread of the virus. While a single immune correlate has not been identified, both antibodies and CD8 T-cell responses contribute to control of infection with HIV or the related simian immunodeficiency virus (SIV) and disease progression (5, 17, 23, 28, 35-39, 43, 46, 58). Appropriately designed envelope immunogens able to induce broad, potent neutralizing antibodies have not yet been achieved, but vaccine-elicited virus-specific cellular immune responses have been more readily elicited. Both DNA and recombinant viral vectors have emerged as prominent candidate vaccines for this purpose. Although DNA vaccines are not as immunogenic as other vectored vaccines, a variety of approaches can enhance their potency (20). Further, the striking observations that DNA priming followed by boosting with an adenovirus (Ad) or modified vaccinia virus Ankara (MVA)-vectored vaccine elicits enhanced immunity and protective efficacy (3, 59) suggest that among many available vectors (27) other DNA-vector combinations might be equally or more potent.Increasing knowledge of cytokine networks and their influences on the immune system has provided new opportunities for vaccine design and propelled the field toward tailored immune responses. IL-12, first described as natural killer (NK) cell stimulatory factor (25), and IL-15 (18) are among promising candidate cytokine adjuvants for directing such tailored immune responses. Both interleukins have strong effects on NK cells and T cells, influencing the magnitude and quality of cellular responses (1,4,15,30,63). IL-12 acts as adjuvant for both CD4 and CD8 T-cell responses. When administered as a DNA expression vector in combination with other DNA vaccines, it increased cellular immunity in mice (24) and enhanced both humoral and cellular immune responses in rhesus macaques (11,13,57,61). Recently, the addition of IL-12 DNA plasmids to a SIVgag DNA vaccine regimen and to a prime/ boost DNA/vesicular stomatitis virus-SIVgag regimen increased protective efficacy against a SHIV 89.6P challenge (11,13). IL-15, in contrast, primarily increases cellular immunity and is important for development of memory T cells (44).

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“…Although we were not able to demonstrate its critical role in cell-mediated immunity in HIV-infected patients in our experiments, these observations suggest that IL-12p70 could constitute a potent vaccine adjuvant in situations that may require both arms of the immune system, such as HIV [68]. Indeed, studies with rhesus macaques have concluded that IL-12p70 enhances the induction of specific antibody responses in vivo when used as vaccine adjuvant [69–71]. On the other hand, Traxlmayr et al revealed a potential negative effect of peripheral blood γδ T cells on CD4 + and CD8 + immune responses in cancer patients undergoing immune therapy with IL-12p70-secreting DCs [72].…”

Section: Discussionmentioning

confidence: 89%

Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulategag-Specific Immune Responses

Gulck

Cools

Atkinson

et al. 2012

Clinical and Developmental Immunology

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A variety of immune-based therapies has been developed in order to boost or induce protective CD8+T cell responses in order to control HIV replication. Since dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique capability to stimulate naïve T cells into effector T cells, their use for the induction of HIV-specific immune responses has been studied intensively. In the present study we investigated whether modulation of the activation state of DCs electroporated with consensus codon-optimized HxB2gagmRNA enhances their capacity to induce HIVgag-specific T cell responses. To this end, mature DCs were (i) co-electroporated with mRNA encoding interleukin (IL)-12p70 mRNA, or (ii) activated with a cytokine cocktail consisting of R848 and interferon (IFN)-γ. Our results confirm the ability of HxB2gag-expressing DCs to expand functional HIV-specific CD8+T cells. However, although most of the patients had detectablegag-specific CD8+T cell responses, no significant differences in the level of expansion of functional CD8+T cells could be demonstrated when comparing conventional or immune-modulated DCs expressing IL-12p70. This result which goes against expectation may lead to a re-evaluation of the need for IL-12 expression by DCs in order to improve T-cell responses in HIV-1-infected individuals.

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Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques

Cited by 16 publications

References 26 publications

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge

Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulategag-Specific Immune Responses

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Stimulation of both humoral and cellular immune responses to HIV-1 gp120 by interleukin-12 in Rhesus macaques

Cited by 16 publications

References 26 publications

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12

Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251Mucosal Challenge

Interleukin-12p70 Expression by Dendritic Cells of HIV-1-Infected Patients Fails to Stimulategag-Specific Immune Responses

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Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIV_mac251Mucosal Challenge