This study evaluated the safety, immunogenicity, and preliminary assessment of efficacy of a novel vaccine encoding conserved elements (CE) of the HIV-1 Gag core protein, p24Gag, as a therapeutic vaccine in HIV-1 infected persons who were on antiretroviral therapy (ART). The study aimed to induce potent virus-specific cytotoxic T lymphocytes (CTL) responses.

开始日期2019-03-26

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT03181789 / Completed临床1期IIT

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA, in Healthy, HIV-Uninfected Adult Participants

The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of two HIV-1 pDNA vaccines: p24CE1/2 pDNA and p55^gag pDNA administered with IL-12 pDNA adjuvant, given by intramuscular (IM) injection with electroporation (EP), in healthy, HIV-uninfected adults.

开始日期2017-10-18

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 p55 gag pDNA vaccine(NIAID) 相关的临床结果

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100 项与 p55 gag pDNA vaccine(NIAID) 相关的转化医学

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项与 p55 gag pDNA vaccine(NIAID) 相关的文献（医药）

2023-01-01·Journal of immunological techniques in infectious diseases

Adjuvant effect of dendritic cells activator Imiquimod in genetic immunization with HIV-1 p55 Gag.

Article

作者: Hunter-Mellado, Robert ; Maldonado-Martinez, Gerónimo ; Tsytsarev, Vassiliy ; Roldan-Kalil, Joshua A ; Ramos-Feliciano, Karla M ; Miranda-Valentin, Eric ; Alves, Janaina M ; Inyushin, Mikhail

Dendritic cells (DC) are important antigen-presenting cells that have abilities to induce and maintain T-cell immunity, or attenuate it during hyperimmunization. Additional activation of DCs may be useful for vaccination purposes. Imiquimod is known to be a specific agonist of the Toll-like receptors (TLR7), which are located mainly on DCs. To study the effect of DC stimulation on the effectiveness of an HIV-1 p55 gag DNA vaccine in a mice model, we employed 25, 50, and 100 nM of Imiquimod as an adjuvant. Subsequently, Western blot analysis was used to quantify p55 protein production after the immunization. To characterize T-cells immune response, both the frequency of IFN-γ -secreting cells and IFN-γ and IL-4 production were measured, via an ELIspot assay and ELISA, respectively. Low concentrations of Imiquimod were found to effectively stimulate Gag production and the magnitude of the T-cell immune response, whereas higher concentrations reduced vaccination effects. Our results show that the adjuvant effects of Imiquimod depend on concentration. The use of Imiquimod may be helpful to study DC to T cell communication, including possible induction of immunotolerance.

2018-01-15·Journal of Virology2区 · 医学

Combination Adenovirus and Protein Vaccines Prevent Infection or Reduce Viral Burden after Heterologous Clade C Simian-Human Immunodeficiency Virus Mucosal Challenge

2区 · 医学

Article

作者: Owuor, Joshua ; Forthal, Donald N. ; Montefiori, David ; Haynes, Barton F. ; Gurwith, Marc ; Smith, Jonathan ; Liao, Hua-Xin ; Stapleton, Jack T. ; Axthelm, Michael K. ; Malherbe, Delphine C. ; Xiang, Jinhua ; Alexander, Jeff ; LaBranche, Celia C. ; Legasse, Alfred W. ; Haigwood, Nancy L. ; Gach, Johannes S. ; Barnette, Philip T. ; McLinden, James H. ; Wilson, James M. ; Park, Byung ; Lakhashe, Samir K. ; Mendy, Jason ; Vang, Lo ; Reed, Jason ; Ruprecht, Ruth M. ; Sacha, Jonah B.

ABSTRACTHIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of adenovirus (Ad) vectors expressing HIV 1086.C (clade C) envelope glycoprotein (Env), SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with nonreplicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge. In both vaccine groups, plasma and buccal Env-specific IgG, tier 1 heterologous neutralizing antibodies, and antibody-dependent cell-mediated viral inhibition were readily generated. High Env-specific T cell responses elicited in all vaccinees were significantly greater than responses targeting Gag. After three intrarectal exposures to heterologous tier 1 clade C SHIV, all 10 sham-vaccinated controls were infected, whereas 4/10 SAd7- and 3/10 Ad4-vaccinated macaques remained uninfected or maintained tightly controlled plasma viremia. Time to infection was significantly delayed in SAd7-vaccinated macaques compared to the controls. Cell-associated and plasma virus levels were significantly lower in each group of vaccinated macaques compared to controls; the lowest plasma viral burden was found in animals vaccinated with the SAd7 vectors, suggesting superior immunity conferred by the replicating simian vectors. Furthermore, higher V1V2-specific binding antibody titers correlated with viral control in the SAd7 vaccine group. Thus, recombinant Ad plus protein vaccines generated humoral and cellular immunity that was effective in either protecting from SHIV acquisition or significantly reducing viremia in animals that became infected, consequently supporting additional development of replicating Ad vectors as HIV vaccines.IMPORTANCE There is a well-acknowledged need for an effective AIDS vaccine that protects against HIV infection and limits in vivo viral replication and associated pathogenesis. Although replicating virus vectors have been advanced as HIV vaccine platforms, there have not been any direct comparisons of the replicating to the nonreplicating format. The present study directly compared the replicating SAd7 to nonreplicating Ad4 vectors in macaques and demonstrated that in the SAd7 vaccine group, the time to infection was significantly delayed compared to the control group, and V1V2 Env-specific binding antibodies correlated with viral outcomes. Viral control was significantly enhanced in vaccinated macaques compared to controls, and in infected SAd7-vaccinated macaques compared to Ad4-vaccinated macaques, suggesting that this vector may have conferred more effective immunity. Because blocking infection is so difficult with current vaccines, development of a vaccine that can limit viremia if infection occurs would be valuable. These data support further development of replicating adenovirus vectors.

2017-02-15·Journal of Virology2区 · 医学

Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5α Restrictive Macaques

2区 · 医学

Article

作者: Kozlowski, Pamela A. ; Crotty, Shane ; Kovalenkov, Yevgeniy ; Burton, Samantha L. ; Bosinger, Steven E. ; Nabi, Rafiq ; Burger, Matheus C. ; Pulendran, Bali ; Kasturi, Sudhir Pai ; Sher, Zarpheen Jinnah ; Amara, Rama R. ; Villinger, Francois ; Havenar-Daughton, Colin ; Spearman, Paul ; Wrammert, Jens ; Derdeyn, Cynthia A. ; Pham, Mathew ; Russo, Pedro ; Hunter, Eric ; Kilgore, Katie M. ; Johnson, Mathew J. ; Chen, Xuemin ; Silveira, Eduardo L. V. ; Nakaya, Helder I. ; Legere, Traci

ABSTRACTOur previous work has shown that antigens adjuvanted with ligands specific for Toll-like receptor 4 (TLR4) and TLR7/8 encapsulated in poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NPs) induce robust and durable immune responses in mice and macaques. We investigated the efficacy of these NP adjuvants in inducing protective immunity against simian immunodeficiency virus (SIV). Rhesus macaques (RMs) were immunized with NPs containing TLR4 and TLR7/8 agonists mixed with soluble recombinant SIVmac239-derived envelope (Env) gp140 and Gag p55 (protein) or with virus-like particles (VLPs) containing SIVmac239 Env and Gag. NP-adjuvanted vaccines induced robust innate responses, antigen-specific antibody responses of a greater magnitude and persistence, and enhanced plasmablast responses compared to those achieved with alum-adjuvanted vaccines. NP-adjuvanted vaccines induced antigen-specific, long-lived plasma cells (LLPCs), which persisted in the bone marrow for several months after vaccination. NP-adjuvanted vaccines induced immune responses that were associated with enhanced protection against repeated low-dose, intravaginal challenges with heterologous SIVsmE660 in animals that carried TRIM5α restrictive alleles. The protection induced by immunization with protein-NP correlated with the prechallenge titers of Env-specific IgG antibodies in serum and vaginal secretions. However, no such correlate was apparent for immunization with VLP-NP or alum as the adjuvant. Transcriptional profiling of peripheral blood mononuclear cells isolated within the first few hours to days after primary vaccination revealed that NP-adjuvanted vaccines induced a molecular signature similar to that induced by the live attenuated yellow fever viral vaccine. This systems approach identified early blood transcriptional signatures that correlate with Env-specific antibody responses in vaginal secretions and protection against infection. These results demonstrate the adjuvanticity of the NP adjuvant in inducing persistent and protective antibody responses against SIV in RMs with implications for the design of vaccines against human immunodeficiency virus (HIV).IMPORTANCE The results of the RV144 HIV vaccine trial, which demonstrated a rapid waning of protective immunity with time, have underscored the need to develop strategies to enhance the durability of protective immune responses. Our recent work in mice has highlighted the capacity of nanoparticle-encapsulated TLR ligands (NP) to induce potent and durable antibody responses that last a lifetime in mice. In the present study, we evaluated the ability of these NP adjuvants to promote robust and durable protective immune responses against SIV in nonhuman primates. Our results demonstrate that immunization of rhesus macaques with NP adjuvants mixed with soluble SIV Env or a virus-like particle form of Env (VLP) induces potent and durable Env-specific antibody responses in the serum and in vaginal secretions. These responses were superior to those induced by alum adjuvant, and they resulted in enhanced protection against a low-dose intravaginal challenge with a heterologous strain of SIV in animals with TRIM5a restrictive alleles. These results highlight the potential for such NP TLR L adjuvants in promoting robust and durable antibody responses against HIV in the next generation of HIV immunogens currently being developed.

100 项与 p55 gag pDNA vaccine(NIAID) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
获得性免疫缺陷综合征	临床2期	美国	National Institute of Allergy & Infectious Diseases	2019-01-29
获得性免疫缺陷综合征	临床2期	波多黎各	National Institute of Allergy & Infectious Diseases	2019-01-29

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03560258 (CTgov)	临床1/2期	HIV感染	45	p24CE1/2 pDNA vaccine+p55^gag pDNA vaccine (Arm A: p24CE/Full-length Gag DNA)	鑰願鑰齋範顧膚蓋鹽齋(願選願觸積遞構襯餘廠) = 築壓選蓋壓願醖願積襯鏇鑰艱顧齋窪選衊構醖 (夢襯築醖淵憲積選積願, 網膚淵衊鹽糧齋顧鹽鬱 ~ 艱齋壓醖淵廠餘壓鑰選) 更多	-	2022-04-26
				full-length p55^gag pDNA vaccine (Arm B: Full-length Gag DNA)	鑰願鑰齋範顧膚蓋鹽齋(願選願觸積遞構襯餘廠) = 製獵願齋膚艱憲夢鏇鑰鏇鑰艱顧齋窪選衊構醖 (夢襯築醖淵憲積選積願, 襯窪廠選艱顧壓範願顧 ~ 艱鹽餘艱鹹範醖觸蓋網) 更多