Michalek S M, Morisaki I, Gregory R L, Kiyono H, Hamada S, McGhee J R
Mol Immunol. 1983 Sep;20(9):1009-18. doi: 10.1016/0161-5890(83)90042-1.
The induction of immune responses to orally-administered trinitrophenyl (TNP)-haptenated Streptococcus mutans or its cell wall components and enhancement of immune responses with oral adjuvants has been studied in high IgA responsive C3H/HeJ mice and in gnotobiotic rats. Gastric intubation of TNP-S. mutans to LPS non-responsive C3H/HeJ or syngeneic, LPS responsive C3H/HeN mice induced IgA responses as determined by measuring splenic plaque-forming cell (PFC) responses and IgA anti-TNP antibodies in serum, saliva, and urine. Higher IgA responses always occurred in C3H/HeJ mice given oral S. mutans antigen than similarly treated C3H/HeN animals. Oral administration of the adjuvants concanavalin A or S. mutans cell wall peptidoglycan (PG) with antigen resulted in augmented IgA responses, especially in C3H/HeJ mice. On the other hand, oral administration of muramyl dipeptide (MDP) with antigen boosted anti-TNP responses in C3H/HeN, but not in C3H/HeJ, mice. Gnotobiotic rats given S. mutans whole cells (WC) or purified cell walls (CW) by the oral route exhibited a salivary IgA immune response which was potentiated greater than twofold when antigen was given with PG or MDP. In other studies, S. mutans WC or CW antigen in water-oil-water (W/O/W) emulsion or liposomes was administered by gastric intubation to rats. Significant salivary IgA responses were induced with these antigen-adjuvant preparations. Although rats given S. mutans WC or CW were protected from S. mutans challenge, the greatest degree of caries immunity was obtained in animals which received antigen and adjuvant and which exhibited significant salivary IgA antibody levels. In preliminary studies, it was observed that local injection of rats in the salivary gland region with a ribosomal preparation from S. mutans resulted in a significant salivary IgA response and caries immunity. The potential for soluble and lipid carrier adjuvants in oral vaccines for induction of protective antibodies to S. mutans is discussed.
在高IgA反应性的C3H/HeJ小鼠和无菌大鼠中，研究了口服三硝基苯基（TNP）偶联变形链球菌或其细胞壁成分诱导免疫反应以及口服佐剂增强免疫反应的情况。将TNP-变形链球菌经胃管投予LPS无反应性的C3H/HeJ或同基因、LPS反应性的C3H/HeN小鼠，通过测量脾空斑形成细胞（PFC）反应以及血清、唾液和尿液中的IgA抗TNP抗体来确定是否诱导了IgA反应。给予口服变形链球菌抗原的C3H/HeJ小鼠总是比同样处理的C3H/HeN动物产生更高的IgA反应。口服伴刀豆球蛋白A或变形链球菌细胞壁肽聚糖（PG）佐剂与抗原一起使用，会增强IgA反应，尤其是在C3H/HeJ小鼠中。另一方面，口服胞壁酰二肽（MDP）与抗原一起使用，可增强C3H/HeN小鼠而非C3H/HeJ小鼠的抗TNP反应。经口服途径给予无菌大鼠变形链球菌全细胞（WC）或纯化细胞壁（CW），当抗原与PG或MDP一起给予时，会表现出唾液IgA免疫反应，且增强了两倍以上。在其他研究中，通过胃管将水包油包水（W/O/W）乳液或脂质体中的变形链球菌WC或CW抗原给予大鼠。这些抗原-佐剂制剂诱导了显著的唾液IgA反应。尽管给予变形链球菌WC或CW的大鼠受到了变形链球菌攻击的保护，但在接受抗原和佐剂且唾液IgA抗体水平显著的动物中获得了最大程度的龋齿免疫力。在初步研究中，观察到在唾液腺区域局部注射来自变形链球菌的核糖体制剂可导致显著的唾液IgA反应和龋齿免疫力。讨论了可溶性和脂质载体佐剂在口服疫苗中诱导针对变形链球菌的保护性抗体的潜力。
