The CAG hybrid promoter improved not only the expression level, but also the immunogenicity of the fusion protein, and may thus provide a promising strategy for HTNV vaccine research.
Hydropericardium syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) poses a severe threat to global poultry production. Although inactivated vaccines are widely used, they may elicit suboptimal cellular immune responses and provide incomplete protection. In this study, six candidate immunostimulants were compared for their ability to enhance the immunogenicity and protective efficacy of an inactivated FAdV-4 vaccine. Among the formulations and doses evaluated, the chicken interleukin-2-interferon-α fusion protein (chIL2-IFNα) produced the strongest overall response. At 21 dpi, the chIL2-IFNα-supplemented group reached a mean peak neutralizing-antibody titer of 9.28 log2, significantly exceeding the 4.19 log2 observed in the vaccine-only group (P < 0.05). This formulation also increased the frequencies of phenotypically defined natural killer cells and cytotoxic T lymphocytes and upregulated cytotoxic-effector-gene expression. Following FAdV-4 challenge, 9 of 10 chickens (90%) in the chIL2-IFNα-supplemented group survived to 14 dpc, compared with 3 of 10 chickens (30%) in the vaccine-only group. The mean liver viral load was 5.85 log10 copies/μL lower than that in the vaccine-only group, accompanied by reduced viral shedding and less severe tissue lesions. These findings support further evaluation of chIL2-IFNα as an immunostimulant for inactivated FAdV-4 vaccines.
Peng Chen, Yanan Cui, Longhai Ji et al.· International Journal of Bio...· 0 citations
ABSTRACT With the broad spread of the chikungunya virus (CHIKV), there is an increasing demand for more effective and protective vaccines. In this study, we first developed a Newcastle disease virus (NDV) vector vaccine candidate expressing the complete envelope (E3–E1) protein of CHIKV. The immunoelectron microscopy confirmed the presence of E2 protein in the rNDV-CHIKV virion, and the virological results showed that the expression of E1 and E2 protein was stable after 10 serial passages in embryonated chicken eggs. Moreover, we assessed its safety and immunogenicity following intramuscular (i.m.) or subcutaneous (s.c.) administration in C57BL/6 mice. The immunogenicity analyses demonstrated that a single-dose immunization elicits high titers of CHIKV E2-specific IgG antibodies, potent neutralizing activity, and T-cell immune responses. Importantly, both routes of immunization conferred complete protection against wild-type CHIKV challenge in C57BL/6 mice. These findings present a promising novel vector-based vaccine candidate with significant potential for effective CHIKV prevention. IMPORTANCE Chikungunya virus (CHIKV) imposes a substantial global health burden, characterized by arthralgia that can persist for years, neurological complications, and potentially fatal outcomes in vulnerable populations. Currently, two vaccines against CHIKV have been approved: a live-attenuated vaccine (Ixchiq) and a virus-like particle (VLP) vaccine (Vimkunya). However, Ixchiq has been withdrawn from clinical use due to significant side effects, highlighting the urgent need for the development of novel vaccine strategies. Our research has successfully developed a novel vaccine candidate that utilizes Newcastle disease virus as a vector to express CHIKV antigens. This innovative strategy offers multiple advantages: cost-effectiveness, genetic stability of the inserted gene, and robust immunogenicity with effective immune protection. This approach offers a contribution in addressing the emerging threat posed by CHIKV. Chikungunya virus (CHIKV) imposes a substantial global health burden, characterized by arthralgia that can persist for years, neurological complications, and potentially fatal outcomes in vulnerable populations. Currently, two vaccines against CHIKV have been approved: a live-attenuated vaccine (Ixchiq) and a virus-like particle (VLP) vaccine (Vimkunya). However, Ixchiq has been withdrawn from clinical use due to significant side effects, highlighting the urgent need for the development of novel vaccine strategies. Our research has successfully developed a novel vaccine candidate that utilizes Newcastle disease virus as a vector to express CHIKV antigens. This innovative strategy offers multiple advantages: cost-effectiveness, genetic stability of the inserted gene, and robust immunogenicity with effective immune protection. This approach offers a contribution in addressing the emerging threat posed by CHIKV.
Qiu-Yan Zhang, Yang Zhang, Zhe-Rui Zhang et al.· Journal of Virology· 0 citations
Dengue virus (DENV) nonstructural protein 3 (NS3) is essential for viral replication and host immune evasion. While its protease domain (NS3pro) has been linked to T-cell anergy, its role in inducing regulatory T cells (Tregs) requires further exploration. To analyze the induction of diverse regulatory T-cell populations in BALB/c mice immunized with recombinant rNS3pro proteins from the four DENV serotypes. Mice were immunized with rNS3pro, and splenocytes were stimulated in vitro with homologous proteins. Cytokine expression and T-cell phenotypes-including markers for activation, exhaustion, and cytotoxicity-were analyzed via RT-PCR, ELISA, and flow cytometry. rNS3pro immunization induced a predominantly regulatory-associated response characterized by significant IL-10 expression. A marked expansion of CD4+CD25+ T cells (23.5% vs. 1.05% in controls) was observed, encompassing CD25+FoxP3+ regulatory-like T cells, alongside FoxP3-independent subsets expressing CD25+IL-10+ and CD25+TGF-β+. These cells co-expressed cytotoxicity-associated (FoxP3+Perforin+/GzB+) and co-inhibitory (CTLA-4+, PD-1+) markers. Effector CD8+ T-cell proliferation was significantly inhibited and could not be restored by exogenous IL-2. In conclusion, DENV rNS3pro immunization drives a robust expansion of multifaceted regulatory-like T-cell phenotypes. This immunomodulatory response correlates with compromised CD8+ effector proliferation, identifying the NS3 protease domain as a potential player in DENV immune evasion strategies.
V. Romero-Cruz, Á. Ramos-Ligonio, Diana Lizzet Murrieta-León et al.· Acta Tropica· 0 citations
The HEK293T model stably expressing membrane-anchored HIV-1 gp160(ΔCT) model provides a robust platform for benchmarking the targeted recognition and cytotoxic activity of antiviral antibodies, agents, and CAR-T therapies in HIV research.
Jiarui Liu, Yang Gao, Changjun Wang et al.· Sheng wu gong cheng xue bao...· 0 citations
The recombinant virus maintained wild-type-comparable titers while carrying 3606 bp of total foreign sequences, highlighting its dual-site advantage and potential as a multivalent poultry vaccine vector.
It is demonstrated that NTV-ΔF1L-C7L combines high safety with enhanced replication and immunogenicity, supporting its value as a novel vaccine vector and its potential application in controlling the current global monkeypox outbreak.
Jiao Ren, Shi-Yuan Liu, Hang Yuan et al.· Journal of Virology· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
