Killar L M, Eisenstein T K
Infect Immun. 1985 Mar;47(3):605-12. doi: 10.1128/iai.47.3.605-612.1985.
Immunization with avirulent Salmonella typhimurium strain SL3235, a smooth, aroA- derivative, was shown to induce high levels of resistance to challenge with virulent S. typhimurium in innately hypersusceptible C3H/HeJ mice and inherently resistant C3H/HeNCrlBR mice. Strain SL3235 is one of a class of avirulent aroA- derivatives made from various strains and species of Salmonella that are being considered as vaccine candidates for cattle and humans. This paper supports their efficacy and potential utility in this regard. In C3H/HeJ mice, immunity against over 1,000 50% lethal doses of virulent S. typhimurium was evident as early as 3 days after immunization and persisted for at least 7 months. Further, the vaccine was effective over a broad spectrum of doses, ranging from 10(4) to 10(6) organisms. Infection with SL3235 led to marked splenomegaly in both mouse strains. The relationship of splenomegaly to the growth kinetics and colonization by SL3235 in the spleens of infected C3H/HeJ and C3H/HeNCrlBR mice was followed. SL3235 initially multiplied slowly in the spleens of both mouse strains and then was rapidly cleared. Less multiplication was seen in the resistant C3H/HeNCrlBR mice than in C3H/HeJ mice. Maximum splenomegaly occurred after clearance of the organism had begun. Protection against virulent S. typhimurium persisted after virtually all of the SL3235 vaccine strain had been cleared from the spleen. Cross-protection against Listeria monocytogenes was evident, but had a later onset, waned by 21 days, and was not detectable by 1 month after vaccination. Demonstration of this cross-protection is consistent with the interpretation that SL3235 induces cellular immunity. One-week immune spleen cells adoptively transferred anti-S. typhimurium and anti-L. monocytogenes immunity. T cell-enriched fractions were ineffective in adoptive transfer, as were spleen cells taken 2 weeks or later after immunization. Protective capacity was in the adherent cell fraction and seemed to be associated with macrophages. Evidence for induction of a population of sensitized T cells was obtained by using a peritoneal exudate T-lymphocyte proliferation assay on peritoneal T lymphocytes collected 1 to 3 months after SL3235 infection.
用无毒的鼠伤寒沙门氏菌SL3235菌株（一种光滑的aroA衍生物）免疫，结果表明，在先天高度易感的C3H/HeJ小鼠和先天具有抗性的C3H/HeNCrlBR小鼠中，该菌株能诱导产生高水平的抗强毒鼠伤寒沙门氏菌攻击的能力。SL3235菌株是从各种沙门氏菌菌株和物种中制备的一类无毒aroA衍生物之一，正被考虑作为牛和人类的候选疫苗。本文支持它们在这方面的效力和潜在用途。在C3H/HeJ小鼠中，早在免疫后3天就明显产生了针对超过1000个50%致死剂量强毒鼠伤寒沙门氏菌的免疫力，并且持续了至少7个月。此外，该疫苗在10⁴至10⁶个菌的广泛剂量范围内均有效。用SL3235感染导致两种小鼠品系出现明显的脾肿大。研究了感染的C3H/HeJ和C3H/HeNCrlBR小鼠脾脏中脾肿大与SL3235的生长动力学和定植之间的关系。SL3235最初在两种小鼠品系的脾脏中缓慢增殖，然后迅速被清除。在具有抗性的C3H/HeNCrlBR小鼠中观察到的增殖比在C3H/HeJ小鼠中少。在该菌开始被清除后出现最大程度的脾肿大。在几乎所有SL3235疫苗菌株已从脾脏中清除后，对强毒鼠伤寒沙门氏菌的保护作用仍然存在。对单核细胞增生李斯特菌的交叉保护作用明显，但出现较晚，在21天时减弱，在接种后1个月时无法检测到。这种交叉保护作用的证明与SL3235诱导细胞免疫的解释一致。免疫1周的脾细胞可过继转移抗鼠伤寒沙门氏菌和抗单核细胞增生李斯特菌的免疫力。富含T细胞的组分在过继转移中无效，免疫后2周或更晚获取的脾细胞也是如此。保护能力存在于贴壁细胞组分中，似乎与巨噬细胞有关。通过对SL3235感染后1至3个月收集的腹膜T淋巴细胞进行腹膜渗出液T淋巴细胞增殖试验，获得了诱导一群致敏T细胞的证据。
