Cote Christopher K, Biryukov Sergei S, Klimko Christopher P, Shoe Jennifer L, Hunter Melissa, Rosario-Acevedo Raysa, Fetterer David P, Moody Krishna L, Meyer Joshua R, Rill Nathaniel O, Dankmeyer Jennifer L, Worsham Patricia L, Bozue Joel A, Welkos Susan L
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
Vaccines (Basel). 2021 Feb 16;9(2):161. doi: 10.3390/vaccines9020161.
The etiologic agent of plague, , is a globally distributed pathogen which poses both a natural and adversarial threat. Due largely to the rapid course and high mortality of pneumonic plague, vaccines are greatly needed. Two-component protein vaccines have been unreliable and potentially vulnerable to vaccine resistance. We evaluated the safety and efficacy of eight live strains derived from virulent strains CO92 or KIM6+ and mutated in one or more virulence-associated gene(s) or cured of plasmid pPst. Stringent, single-dose vaccination allowed down-selection of the two safest and most protective vaccine candidates, CO92 mutants - pPst- and Δ. Both completely protected BALB/c mice against subcutaneous and aerosol challenge with . Strain CD-1 outbred mice were more resistant to bubonic (but not pneumonic) plague than BALB/c mice, but the vaccines elicited partial protection of CD-1 mice against aerosol challenge, while providing full protection against subcutaneous challenge. A Δ mutant of the nonencapsulated C12 strain was expected to display antigens previously concealed by the capsule. C12 Δ elicited negligible titers to F1 but comparable antibody levels to whole killed bacteria, as did CO92 Δ. Although one dose of C12 Δ was not protective, vaccination with two doses of either CO92 Δ or a combination of the Δysc mutants of C12 and CO92, protected optimally against lethal bubonic or pneumonic plague. Protection against encapsulated required inclusion of F1 in the vaccine and was associated with high anti-F1 titers.
鼠疫的病原体耶尔森菌是一种全球分布的病原体，构成自然和对抗性威胁。由于肺鼠疫病程进展迅速且死亡率高，非常需要疫苗。双组分蛋白疫苗一直不可靠，且可能易产生疫苗抗性。我们评估了八种源自强毒株CO92或KIM6 +且一个或多个毒力相关基因发生突变或质粒pPst缺失的减毒活菌株的安全性和有效性。严格的单剂量疫苗接种使得能够筛选出两种最安全、保护性最强的候选疫苗，即CO92突变株 - pPst-和Δ。二者均能完全保护BALB/c小鼠免受耶尔森菌的皮下和气溶胶攻击。CD-1远交系小鼠比BALB/c小鼠对腺鼠疫（但不是肺鼠疫）更具抗性，但这些疫苗能使CD-1小鼠在气溶胶攻击中获得部分保护，同时对皮下攻击提供完全保护。预计非包膜C12菌株的Δ突变株会呈现出先前被包膜掩盖的抗原。C12 Δ诱导产生的F1抗体效价可忽略不计，但与全菌灭活疫苗产生的抗体水平相当，CO92 Δ也是如此。虽然一剂C12 Δ没有保护作用，但接种两剂CO92 Δ或C12和CO92的Δysc突变株组合能最佳地预防致死性腺鼠疫或肺鼠疫。预防包膜耶尔森菌感染需要在疫苗中包含F1，且与高抗F1抗体效价相关。
