Techawiwattanaboon Teerasit, Barnier-Quer Christophe, Palaga Tanapat, Jacquet Alain, Collin Nicolas, Sangjun Noppadon, Komanee Pat, Patarakul Kanitha
Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand.
Vaccines (Basel). 2020 Sep 1;8(3):494. doi: 10.3390/vaccines8030494.
Leptospirosis vaccines with higher potency and reduced adverse effects are needed for human use. The carboxyl terminal domain of leptospiral immunoglobulin like protein A (LigAc) is currently the most promising candidate antigen for leptospirosis subunit vaccine. However, LigAc-based vaccines were unable to confer sterilizing immunity against infection in animal models. Several factors including antigen properties, adjuvant, delivery system, and administration route need optimization to maximize vaccine efficacy. Our previous report demonstrated protective effects of the recombinant LigAc (rLigAc) formulated with liposome-based adjuvant, called LMQ (neutral liposome combined with monophosphoryl lipid A and fraction 21) in hamsters. This study aimed to evaluate the impact of two commonly used administration routes, intramuscular (IM) and subcutaneous (SC), on immunogenicity and protective efficacy of rLigAc-LMQ administrated three times at 2-week interval. Two IM vaccinations triggered significantly higher levels of total anti-rLigAc IgG than two SC injections. However, comparable IgG titers and IgG2/IgG1 ratio was observed for both routes after the third immunization. The route of vaccine administration did not influence the survival rate (60%) and renal colonization against lethal challenge. Importantly, the kidneys of IM group showed no pathological lesions while the SC group showed mild damage. In conclusion, IM vaccination with rLigAc-LMQ not only elicited faster antibody production but also protected from kidney damage following leptospiral infection better than SC immunization. However, both tested routes did not influence protective efficacy in terms of survival rate and the level of renal colonization.
人类需要效力更高、副作用更小的钩端螺旋体病疫苗。钩端螺旋体免疫球蛋白样蛋白A（LigAc）的羧基末端结构域是目前钩端螺旋体病亚单位疫苗最有前景的候选抗原。然而，基于LigAc的疫苗在动物模型中无法提供针对感染的杀菌免疫力。包括抗原特性、佐剂、递送系统和给药途径在内的几个因素需要优化，以最大限度地提高疫苗效力。我们之前的报告证明了用基于脂质体的佐剂LMQ（中性脂质体与单磷酰脂质A和21组分结合）配制的重组LigAc（rLigAc）在仓鼠中的保护作用。本研究旨在评估两种常用给药途径，即肌肉注射（IM）和皮下注射（SC），对每隔2周接种三次的rLigAc-LMQ的免疫原性和保护效力的影响。两次IM接种引发的总抗rLigAc IgG水平明显高于两次SC注射。然而，第三次免疫后，两种途径的IgG滴度和IgG2/IgG1比值相当。疫苗接种途径不影响生存率（60%）和针对致死性攻击的肾脏定植。重要的是，IM组的肾脏没有病理损伤，而SC组有轻度损伤。总之，用rLigAc-LMQ进行IM接种不仅能更快地产生抗体，而且在钩端螺旋体感染后比SC免疫更好地保护免受肾脏损伤。然而，就生存率和肾脏定植水平而言，两种测试途径都不影响保护效力。
