Williams J C, Peacock M G, Waag D M, Kent G, England M J, Nelson G, Stephenson E H
Office of the Scientific Director, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland 20982.
Ann N Y Acad Sci. 1992 Jun 16;653:88-111. doi: 10.1111/j.1749-6632.1992.tb19633.x.
We have demonstrated the safety, immunogenicity, and efficacy of the WC and CMR vaccines in guinea pigs. Vaccination of guinea pigs with either WC or CMR protects animals against challenge with virulent C. burnetii. A total of 2 micrograms of either WC or CMR vaccine was a significant priming dose. A total of 20 micrograms gave complete protection against lethal challenge. Detection of antibodies to phase II cells by microaglutination, after vaccination with either WC or CMR and before lethal challenge, correlated with the ability of guinea pigs to mount a protective immune response. The PD50 values for WC and CMR vaccines, administered as a single dose, were 0.3 and 1.4 micrograms per animal, respectively. In contrast, the PD50 values for the WC and CMR vaccines, administered as two doses, were 0.83 and 0.72 micrograms per animal, respectively. Although the PD50 values for the two vaccines are similar, the CMR vaccine is preferred over the WC vaccine because it induces significantly fewer adverse reactions, and repeat injections can be given. Unvaccinated guinea pigs do not clear infectious microorganisms after challenge infection. Vaccination before challenge infection reduces the infectious load of C. burnetti in the blood and in various organs of the animals. When vaccinated animals were challenge infected and treated with rifampicin, the microorganisms were not eliminated from various organs. However, the combination of vaccination, challenge, and rifampicin treatment is effective in reducing the number of infectious microorganisms in some of these sites. We have demonstrated the safety and immunogenicity of the CMR vaccine in sheep and goats. Animals that were seropositive for one or more antigens developed significant levels of antibodies to alternate antigens, but no adverse reactions were observed at the site of s.c. injection of the CMR vaccine. This demonstrates that seropositive animals can be successfully immunized with this vaccine. These results also indicate that a long-term vaccination program using the CMR vaccine has the potential for producing animals with significant antibody titers to C. burnetii and perhaps lifelong immunity. The goal of a Q fever vaccination program is to produce immunized animals that are able to clear completely the infectious microorganisms. The appropriate vaccination schedule to render adult animals and their offspring "Q fever-free" should now be thoroughly investigated.
我们已经在豚鼠身上证明了WC疫苗和CMR疫苗的安全性、免疫原性和有效性。用WC疫苗或CMR疫苗对豚鼠进行接种可保护动物免受强毒力伯纳特立克次体的攻击。2微克的WC疫苗或CMR疫苗均为显著的起始剂量。20微克可提供完全的保护，使其免受致死性攻击。在接种WC疫苗或CMR疫苗后、致死性攻击前，通过微量凝集试验检测针对II期细胞的抗体，这与豚鼠产生保护性免疫反应的能力相关。单剂量接种时，WC疫苗和CMR疫苗的PD50值分别为每只动物0.3微克和1.4微克。相比之下，两剂量接种时，WC疫苗和CMR疫苗的PD50值分别为每只动物0.83微克和0.72微克。尽管两种疫苗的PD50值相似，但CMR疫苗比WC疫苗更受青睐，因为它引起的不良反应显著较少，且可进行重复注射。未接种疫苗的豚鼠在受到攻击感染后无法清除感染性微生物。在攻击感染前进行接种可降低动物血液和各个器官中伯纳特立克次体的感染负荷。当对接种疫苗的动物进行攻击感染并用利福平治疗时，微生物并未从各个器官中清除。然而，接种疫苗、进行攻击感染和利福平治疗的联合应用在减少其中一些部位的感染性微生物数量方面是有效的。我们已经在绵羊和山羊身上证明了CMR疫苗的安全性和免疫原性。对一种或多种抗原呈血清阳性的动物产生了针对其他抗原的显著水平的抗体，但在皮下注射CMR疫苗的部位未观察到不良反应。这表明血清阳性动物可以成功接种这种疫苗。这些结果还表明，使用CMR疫苗的长期接种计划有可能使动物产生针对伯纳特立克次体的显著抗体滴度，并可能产生终身免疫力。Q热接种计划的目标是培育出能够完全清除感染性微生物的免疫动物。现在应该彻底研究使成年动物及其后代“无Q热”的合适接种时间表。
