Hogenesch Harm, Dunham Anisa, Hansen Bethany, Anderson Kathleen, Maisonneuve Jean-Francois, Hem Stanley L
Department of Comparative Pathobiology, Purdue University, 725 Harrison Street, West Lafayette, IN 47907, USA.
J Immune Based Ther Vaccines. 2011 Jul 29;9:5. doi: 10.1186/1476-8518-9-5.
Streptococcus pneumoniae causes widespread morbidity and mortality. Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. An affordable and broadly protective vaccine is very desirable. The goal of this study was to determine the optimal formulation of a killed whole cell pneumococcal vaccine with aluminum-containing adjuvants for intramuscular injection.
Four aluminium-containing adjuvants were prepared with different levels of surface phosphate groups resulting in different adsorptive capacities and affinities for the vaccine antigens. Mice were immunized three times and the antigen-specific antibody titers and IL-17 responses in blood were analyzed.
Although all adjuvants induced significantly higher antibody titers than antigen without adjuvant, the vaccine containing aluminum phosphate adjuvant (AP) produced the highest antibody response when low doses of antigen were used. Aluminum hydroxide adjuvant (AH) induced an equal or better antibody response at high doses compared with AP. Vaccines formulated with AH, but not with AP, induced an IL-17 response. The vaccine formulated with AH was stable and retained full immunogenicity when stored at 4°C for 4 months.
Antibodies are important for protection against systemic streptococcal disease and IL-17 is critical in the prevention of nasopharyngeal colonization by S. pneumoniae in the mouse model. The formulation of the whole killed bacterial cells with AH resulted in a stable vaccine that induced both antibodies and an IL-17 response. These experiments underscore the importance of formulation studies with aluminium containing adjuvants for the development of stable and effective vaccines.
肺炎链球菌可导致广泛的发病和死亡。目前的疫苗包含游离多糖或蛋白质 - 多糖共轭物，且不能诱导针对疫苗未包含血清型的保护作用。一种价格合理且具有广泛保护作用的疫苗非常令人期待。本研究的目的是确定用于肌肉注射的含铝佐剂的全细胞肺炎球菌灭活疫苗的最佳配方。
制备了四种含铝佐剂，其表面磷酸基团水平不同，导致对疫苗抗原的吸附能力和亲和力不同。对小鼠进行三次免疫，并分析血液中的抗原特异性抗体滴度和IL - 17反应。
尽管所有佐剂诱导产生的抗体滴度均显著高于无佐剂的抗原，但当使用低剂量抗原时，含磷酸铝佐剂（AP）的疫苗产生的抗体反应最高。与AP相比，氢氧化铝佐剂（AH）在高剂量时诱导产生同等或更好的抗体反应。用AH而非AP配制的疫苗诱导了IL - 17反应。用AH配制的疫苗在4°C储存4个月时稳定且保留了完全的免疫原性。
抗体对于预防全身性链球菌疾病很重要，而IL - 17在小鼠模型中预防肺炎链球菌在鼻咽部的定植至关重要。用AH配制的全灭活细菌细胞疫苗产生了一种稳定的疫苗，可诱导抗体和IL - 17反应。这些实验强调了含铝佐剂配方研究对于开发稳定有效疫苗的重要性。
