Zabalza-Baranguá A, Poveda-Urkixo I, Mena-Bueno S, Ramírez G A, De Bolle X, Grilló M J
Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), 31192, Mutilva, Navarra, Spain.
Instituto de Agrobiotecnología (IdAB, CSIC-Gobierno de Navarra), 31192, Mutilva, Navarra, Spain; Universidad Pública de Navarra (UPNA), 31006, Pamplona, Navarra, Spain.
Vaccine. 2023 Feb 24;41(9):1554-1566. doi: 10.1016/j.vaccine.2023.01.017. Epub 2023 Jan 16.
Brucellosis, a worldwide zoonotic disease, is endemic in many developing countries. Besides causing significant economic losses for the livestock industry, it has severe consequences for human health. In endemic regions, small ruminants infected by Brucella melitensis are the main source of human brucellosis. Rev1, the only vaccine currently recommended to control the disease in sheep and goats, has several drawbacks. Rough lipopolysaccharide (R-LPS) mutants have been tested as alternatives, but most lack efficacy. Those in the Wzm/Wzt system responsible for O-polysaccharide export to the periplasm have been proposed as promising vaccine candidates, although to date they have been scarcely investigated in the natural host. In the present work, we studied the biological properties of a 16MΔwzm in-frame deletion mutant, including its safety in pregnant mice and sheep. In mice, 16MΔwzm prevented placental and fetal infections before parturition and protected against B. melitensis and Brucella ovis infections. In sheep, 16MΔwzm was equally safe in lambs, rams, and non-pregnant ewes, inducing some transient Rose Bengal reactions (<7 weeks). The serological reactions occurred earlier and more strongly in pregnant than in non-pregnant ewes and were significantly reduced when conjunctival rather than subcutaneous vaccination was used. In ewes vaccinated at mid-pregnancy, 16MΔwzm was not shed in vaginal discharges during the pregnancy and did not induce abortions/stillbirths. However, some ewes showed a transitory reactivation of infection in placentas and/or milk at parturition, accompanied by a seroconversion in smooth LPS (S-LPS) and/or R-LPS tests. Overall, 16MΔwzm can be considered as a safe vaccine for lambs, rams, and non-pregnant ewes, but its use at mid-pregnancy should be avoided to prevent vaccine dissemination at parturition. If the efficacy results against B. melitensis and B. ovis observed in mice are confirmed by further studies in the natural host, 16MΔwzm could constitute a useful vaccine.
布鲁氏菌病是一种全球性人畜共患病，在许多发展中国家呈地方性流行。它不仅给畜牧业造成重大经济损失，还对人类健康产生严重影响。在流行地区，感染羊种布鲁氏菌的小反刍动物是人类布鲁氏菌病的主要传染源。Rev1是目前唯一推荐用于控制绵羊和山羊布鲁氏菌病的疫苗，但存在一些缺点。粗糙脂多糖（R-LPS）突变体已作为替代疫苗进行测试，但大多数缺乏有效性。负责将O-多糖输出到周质的Wzm/Wzt系统中的突变体被认为是有前景的疫苗候选物，尽管迄今为止它们在天然宿主中的研究很少。在本研究中，我们研究了16MΔwzm框内缺失突变体的生物学特性，包括其在怀孕小鼠和绵羊中的安全性。在小鼠中，16MΔwzm在分娩前可预防胎盘和胎儿感染，并能抵御羊种布鲁氏菌和绵羊布鲁氏菌感染。在绵羊中，16MΔwzm在羔羊、公羊和未怀孕母羊中同样安全，会引发一些短暂的玫瑰红反应（<7周）。血清学反应在怀孕母羊中比未怀孕母羊出现得更早且更强烈，当采用结膜接种而非皮下接种时，反应会显著降低。在怀孕中期接种疫苗的母羊中，16MΔwzm在怀孕期间不会随阴道分泌物排出，也不会引发流产/死产。然而，一些母羊在分娩时胎盘和/或乳汁中出现感染的短暂复发，同时在光滑脂多糖（S-LPS）和/或R-LPS检测中出现血清转化。总体而言，16MΔwzm可被视为羔羊、公羊和未怀孕母羊的安全疫苗，但应避免在怀孕中期使用，以防止分娩时疫苗传播。如果在天然宿主中的进一步研究证实了在小鼠中观察到的16MΔwzm对羊种布鲁氏菌和绵羊布鲁氏菌的有效性结果，那么16MΔwzm可能会成为一种有用的疫苗。
