A Randomised, Placebo-Controlled, Double-Blind, Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Candidate Prophylactic pHIS-HIV-AE DNA Prime and rFPV-HIV-AE Boost HIV Vaccination Strategy

The development of a safe and effective vaccine for HIV is the subject of intensive world-wide research. Various approaches are being investigated in monkey models and humans. This is a randomized, double-blind trial to evaluate the safety and immunogenicity of a candidate preventative human immunodeficiency virus (HIV) vaccine strategy in 24 healthy adult Thai volunteers with no identifiable risk behaviour for HIV-1 infection. Volunteers will receive three "priming" vaccinations at weeks 0, 4 and 8 (pHIS-HIV-AE, a DNA vector delivering AE clade HIV-1 genes). This will be followed at week 12 by single "boost" vaccination (rFPV-HIV-AE, non-replicating, recombinant fowlpox virus vector delivering the same HIV-1 genes). Safety and immunological monitoring will continue to 52 weeks

开始日期2007-08-01

申办/合作机构

Kirby Institute

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100 项与 rFPV-HIV-AE (recombinant fowlpox virus boost) vaccine(Kirby Institute) 相关的临床结果

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100 项与 rFPV-HIV-AE (recombinant fowlpox virus boost) vaccine(Kirby Institute) 相关的转化医学

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100 项与 rFPV-HIV-AE (recombinant fowlpox virus boost) vaccine(Kirby Institute) 相关的专利（医药）

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项与 rFPV-HIV-AE (recombinant fowlpox virus boost) vaccine(Kirby Institute) 相关的文献（医药）

2019-08-01·Vaccine: X

A hierarchical role of IL-25 in ILC development and function at the lung mucosae following viral-vector vaccination

Article

作者: Jackson, R J ; Li, Z ; Ranasinghe, C

This study demonstrates that modulation of IL-25 and IL-33 cytokines responsible for innate lymphoid cell 2 (ILC2) activation/function can differentially regulate ILC profiles at the vaccination site, in a vaccine route-dependent manner. Specifically, recombinant fowlpox (rFPV) vector-based vaccine co-expressing an adjuvant that transiently sequestered IL-25 (FPV-HIV-IL-25 binding protein), delivered intramuscularly (i.m.) was able to induce significantly lower IL-25R⁺ ILC2-deived IL-13 and ILC1/ILC3-derived IFN-γ expression with significantly elevated IL-17A in muscle. In contrast, intranasal (i.n.) delivery was able to induce all three known ILC2 subsets (ST2/IL-33R⁺, IL-25R⁺, and TSLPR⁺ ILC2) to express varying amounts of IL-13 in lung, and also the TSLPR⁺ ILC2 to express IL-4, unlike the unadjuvanted control, which only showed ST2/IL-33R⁺ ILC2 to express IL-13. Interestingly, the sequestration of IL-25 in lung also induced a unique lineage^- ST2/IL-33R^- IL-25R^- TSLPR^- ILC2 population to express elevated IL-13 and IL-4. Moreover, both i.m. and, i.n. FPV-HIV-IL-25BP vaccination induced significantly elevated ILC1/ILC3-derived IL-17A in lung, indicating that ILC2 could directly impact ILC1/ILC3 activity. To our surprise, transient sequestration of IL-33 at the lung mucosae did not alter the lung ILC2 profiles or activity. These inhibitor studies showed that in the context of i.n. viral vector vaccination, IL-25 plays a predominant role in early ILC development/regulation than IL-33, and likely acts as a master regulator of ILC. Our previous findings have indicated that level of IL-4/IL-13 at the vaccination site impacts the quality/avidity of T cell immunity. Taken together data suggest that IL-25 binding protein could be used as an effective i.m. not an i.n. adjuvant to enhance quality of vaccine-specific T cell immunity. These findings evoke the notion that route-dependent manipulation of ILCs according to the target pathogen could be exploited to design more effective vaccines against chronic pathogens in the future.

2019-02-01·Vaccine3区 · 医学

Viral vector and route of administration determine the ILC and DC profiles responsible for downstream vaccine-specific immune outcomes

3区 · 医学

Article

作者: Mahboob, S ; Jaeson, M I ; Wijesundara, D K ; Jackson, R J ; Roy, S ; Gowans, E J ; Grubor-Bauk, B ; Li, Z ; Ranasinghe, C

This study demonstrates that route and viral vector can significantly influence the innate lymphoid cells (ILC) and dendritic cells (DC) recruited to the vaccination site, 24 h post delivery. Intranasal (i.n.) vaccination induced ST2/IL-33R⁺ ILC2, whilst intramuscular (i.m.) induced IL-25R⁺ and TSLPR⁺ (Thymic stromal lymphopoietin protein receptor) ILC2 subsets. However, in muscle a novel ILC subset devoid of the known ILC2 markers (IL-25R^- IL-33R^- TSLPR^-) were found to express IL-13, unlike in lung. Different viral vectors also influenced the ILC-derived cytokines and the DC profiles at the respective vaccination sites. Both i.n. and i.m. recombinant fowlpox virus (rFPV) priming, which has been associated with induction of high avidity T cells and effective antibody differentiation exhibited low ILC2-derived IL-13, high NKp46⁺ ILC1/ILC3 derived IFN-γ and low IL-17A, together with enhanced CD11b⁺ CD103^- conventional DCs (cDC). In contrast, recombinant Modified Vaccinia Ankara (rMVA) and Influenza A vector priming, which has been linked to low avidity T cells, induced opposing ILC derived-cytokine profiles and enhanced cross-presenting DCs. These observations suggested that the former ILC/DC profiles could be a predictor of a balanced cellular and humoral immune outcome. In addition, following i.n. delivery Rhinovirus (RV) and Adenovius type 5 (Ad5) vectors that induced elevated ILC2-derived IL-13, NKp46⁺ ILC1/ILC3-derived-IFN-γ and no IL-17A, predominantly recruited CD11b^- B220⁺ plasmacytoid DCs (pDC). Knowing that pDC are involved in antibody differentiation, we postulate that i.n. priming with these vectors may favour induction of effective humoral immunity. Our data also revealed that vector-specific replication status and/or presence or absence of immune evasive genes can significantly alter the ILC and DC activity. Collectively, our findings suggest that understanding the route- and vector-specific ILC and DC profiles at the vaccination site may help tailor/design more efficacious viral vector-based vaccines, according to the pathogen of interest.

2018-09-01·Indian Journal of Microbiology4区 · 生物学

SIV-Specific Antibodies are Elicited by a Recombinant Fowlpox Virus Co-expressing SIV Gag and envT

4区 · 生物学

Article

作者: Jin, Ningyi ; Wang, Maopeng ; Zhao, Fei ; Du, Shouwen ; Xu, Wang ; Li, Chang ; Zhang, Kelong ; Zhang, Yang ; Zhu, Yilong ; Liu, Jingwei ; Liu, Cunxia ; Guo, Yan ; Ma, Yizhen ; Bai, Jieying ; Bai, Bing ; Cao, Tingting

Given the failures of past HIV-1 vaccine clinical trials, potential HIV-1 vaccine candidates should be rigorously screened in preclinical models including simian immunodeficiency virus (SIV) primate models and small animal models. In this study, we tested the immunogenicity of a recombinant fowlpox virus (rFPV) expressing the SIV gag and SIV envT (rFPV_sg-se) proteins in BALB/c mice, to establish a foundation for further development. rFPV_sg-se was constructed through homologous recombination techniques and purified through plaque screening assays using enhanced green fluorescent protein as the reporter gene. The integration, transcription, and translation of the SIV genes were measured by PCR (genomic DNA), RT-PCR (RNA), Western-blot, respectively. The levels of SIV-specific antibodies were assessed by ELISA following a single immunization (n = 18/group) or a prime-boost strategy (n = 24/group) with rFPV_sg-se and compared to FPV and PBS controls. Residual virus was measured in distant organs following immunization using PCR. SIV-specific IgG titers against gag and gp120 were detected following single vaccination and the prime-boost. As expected the titers were higher following the prime-boost approach. The levels of Gag- and gp120-specific antibodies were significantly higher than controls (p < 0.01) 14 days after the booster immunization. Residual rFPV_Sg-Se was detected in the muscle at the site of injection, but not in distant organs, from day 1-7 post immunization. In summary, rFPV_sg-se induced high levels of SIV-specific antibodies suggesting it may be a viable candidate for further development.

100 项与 rFPV-HIV-AE (recombinant fowlpox virus boost) vaccine(Kirby Institute) 相关的药物交易

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