Sinha Ritam, Howlader Debaki Ranjan, Ta Atri, Mitra Soma, Das Santasabuj, Koley Hemanta
Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, Kolkata, India.
Vaccine. 2017 Jun 16;35(28):3534-3547. doi: 10.1016/j.vaccine.2017.05.036. Epub 2017 May 22.
Bacterial outer membrane vesicles have been extensively investigated and considered as a next generation vaccine. Recently, we have demonstrated that the cholera pentavalent outer membrane vesicles (CPMVs) immunogen induced adaptive immunity and had a strong protective efficacy against the circulating V. cholerae strains in a mouse model. In this present study, we are mainly focusing on reducing outer membrane vesicle (OMV) -mediated toxicity without altering its antigenic property. Therefore, we have selected All-trans Retinoic Acid (ATRA), active metabolites of vitamin A, which have both anti-inflammatory and mucosal adjuvant properties. Pre-treatment of ATRA significantly reduced CPMVs induced TLR2 mediated pro-inflammatory responses in vitro and in vivo. Furthermore, we also found ATRA pre-treatment significantly induced mucosal immune response and protective efficacy after two doses of oral immunization with CPMVs (75µg). This study can help to reduce OMV based vaccine toxicity and induce better protective immunity where children and men suffered from malnutrition mainly in developing countries.
细菌外膜囊泡已被广泛研究，并被视为下一代疫苗。最近，我们已经证明，霍乱五价外膜囊泡（CPMVs）免疫原可诱导适应性免疫，并在小鼠模型中对循环的霍乱弧菌菌株具有强大的保护效力。在本研究中，我们主要致力于在不改变其抗原特性的情况下降低外膜囊泡（OMV）介导的毒性。因此，我们选择了全反式维甲酸（ATRA），它是维生素A的活性代谢产物，具有抗炎和黏膜佐剂特性。ATRA预处理在体外和体内均显著降低了CPMVs诱导的TLR2介导的促炎反应。此外，我们还发现，用CPMVs（75µg）进行两剂口服免疫后，ATRA预处理显著诱导了黏膜免疫反应和保护效力。这项研究有助于降低基于OMV的疫苗毒性，并在主要是发展中国家儿童和男性营养不良的情况下诱导更好的保护性免疫。
