Parenteral Vaccination with a Live Brucella melitensis Mutant Protects against Wild-Type B. melitensis 16M Challenge.
Parenteral Vaccination with a Live Brucella melitensis Mutant Protects against Wild-Type B. melitensis 16M Challenge.
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DOI：
10.3390/microorganisms12010169
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发表时间：
2024-01-15
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
对布鲁氏菌病的易感性仍然很普遍，即使在接种了常规疫苗的牛群中也是如此。目前正在努力开发一种改进的布鲁氏菌病疫苗，并可能开发一种通用疫苗，因为布鲁氏菌属物种具有高度同源性。为此，两个B。开发了羊种黑热病突变体znBM-lacZ（znBMZ）和znBM-mCherry（znBM-mC），并测试了它们赋予针对毒性B的全身免疫的能力。melitensis挑战。为了评估其衰减的程度，用两种突变体感染骨髓来源的巨噬细胞和人TF-1髓样细胞，并注意到这些细胞内无法复制。用不同剂量的znBM-mC感染的小鼠在6-10周内清除了布鲁氏菌。为了测试针对全身性疾病的功效，通过腹膜内途径用znBMZ或B对小鼠组接种一次。流产S19疫苗。相对于PBS给药的小鼠，znBMZ疫苗接种大大降低了脾脏布鲁氏菌定植约25，000倍，而S19疫苗接种的小鼠为700倍。不令人惊讶的是，znBMZ和S19菌株均诱导IFN-γ+ CD 4 + T细胞，但仅znBMZ诱导IFN-γ+ CD 8 + T细胞。虽然两种菌株诱导CD 4+效应记忆T细胞（Tems），但仅znBMZ诱导CD 8 + Tems。因此，这些结果表明所述znBM突变体是安全的，能够引发CD 4+和CD 8 + T细胞免疫而无需加强，并且高度有效，使它们成为有希望的家畜疫苗候选物。
Susceptibility to brucellosis remains prevalent, even in herds vaccinated with conventional vaccines. Efforts are underway to develop an improved brucellosis vaccine, and possibly a universal vaccine, given that Brucella species are highly homologous. To this end, two B. melitensis mutants were developed, znBM-lacZ (znBMZ) and znBM-mCherry (znBM-mC), and were tested for their ability to confer systemic immunity against virulent B. melitensis challenge. To assess the extent of their attenuation, bone-marrow-derived macrophages and human TF-1 myeloid cells were infected with both mutants, and the inability to replicate within these cells was noted. Mice infected with varying doses of znBM-mC cleared the brucellae within 6–10 weeks. To test for efficacy against systemic disease, groups of mice were vaccinated once by the intraperitoneal route with either znBMZ or B. abortus S19 vaccine. Relative to the PBS-dosed mice, znBMZ vaccination greatly reduced splenic brucellae colonization by ~25,000-fold compared to 700-fold for S19-vaccinated mice. Not surprisingly, both znBMZ and S19 strains induced IFN-γ+ CD4+ T cells, yet only znBMZ induced IFN-γ+ CD8+ T cells. While both strains induced CD4+ effector memory T cells (Tems), only znBMZ induced CD8+ Tems. Thus, these results show that the described znBM mutants are safe, able to elicit CD4+ and CD8+ T cell immunity without a boost, and highly effective, rendering them promising vaccine candidates for livestock.
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影响因子：
3.8
作者：
Dean AS;Crump L;Greter H;Schelling E;Zinsstag J
通讯作者：
Zinsstag J
影响因子：
4
作者：
Clapp B;Yang X;Thornburg T;Walters N;Pascual DW
通讯作者：
Pascual DW
影响因子：
2.4
作者：
Olsen, SC;Bricker, B;Cheville, NF
通讯作者：
Cheville, NF
影响因子：
1.2
作者：
Kim, S;Watanabe, K;Watari, M
通讯作者：
Watari, M
影响因子：
3.8
作者：
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通讯作者：
Welburn SC