Wimer-Mackin S, Hinchcliffe M, Petrie C R, Warwood S J, Tino W T, Williams M S, Stenz J P, Cheff A, Richardson C
LigoCyte Pharmaceuticals Inc., 2155 Analysis Drive, Bozeman, MT 59718, USA.
Vaccine. 2006 May 1;24(18):3953-63. doi: 10.1016/j.vaccine.2006.02.024. Epub 2006 Feb 28.
An intranasal vaccine targeting the Bacillus anthracis toxin and vegetative bacterium was tested for the ability to protect immunized rabbits against aerosol B. anthracis spore exposure. Rabbits were vaccinated intranasally with PA-based vaccines formulated as dry powders with or without chitosan (ChiSys, Archimedes Development Limited), a compound that exhibits muco-adhesive properties, or as a liquid. Formulations also contained MPL adjuvant and PA. Some vaccines contained PA conjugated to a 10-mer peptide of the poly-d-glutamic acid capsule of B. anthracis. Rabbits were immunized on days 0 and 28 and aerosol challenged with an average 250LD50 Ames spores on day 85. Serum antibody was measured before and after challenge. Significant anti-PA serum IgG levels were obtained, particularly with use of ChiSys based formulations. PA-Conj induced significant anti-capsule responses, although a formulation containing free capsule peptide did not. All immunized rabbits survived the challenge, but differences in morbidity, as evidenced by anorexia, between vaccine groups were observed. Only rabbits immunized with PA+PA-Conj appeared normal throughout the post-challenge observation period (14 days), while all that received PA with the free capsule peptide appeared ill at times as evidenced by a failure to eat normally. One negative control rabbit received a lower inhaled spore dose (183LD50) and survived the challenge, although it was anorexic post-challenge. It also had a high level of anti-LF antibodies in its convalescent serum (5400 U/ml), indicating an extensive infection. In contrast, 75% of the immunized rabbits had no LF-specific antibody in their post-challenge sera, and the rest had low levels (< or = 138 U/ml), indicating that infections resulting in toxin production were avoided or greatly reduced. Thus, intranasal immunization with a chitosan-based powder vaccine combining PA and capsule epitopes provided superior protection against B. anthracis infection compared to a single antigen (PA) vaccine, as evidenced by a reduction in morbidity and prevention of death.
一种针对炭疽杆菌毒素和繁殖体细菌的鼻内疫苗，被测试用于保护免疫的兔子免受气溶胶形式的炭疽杆菌孢子暴露的影响。兔子通过鼻内接种以干粉形式配制的基于PA的疫苗进行免疫，干粉中添加或不添加壳聚糖（ChiSys，阿基米德发展有限公司），壳聚糖是一种具有粘膜粘附特性的化合物，或者以液体形式接种。制剂中还含有MPL佐剂和PA。一些疫苗含有与炭疽杆菌聚-d-谷氨酸胶囊的10聚体肽偶联的PA。兔子在第0天和第28天进行免疫，并在第85天用平均250LD50的埃姆斯孢子进行气溶胶攻击。在攻击前后测量血清抗体。获得了显著的抗PA血清IgG水平，特别是使用基于ChiSys的制剂时。PA-Conj诱导了显著的抗荚膜反应，尽管含有游离荚膜肽的制剂没有。所有免疫的兔子在攻击中存活下来，但观察到疫苗组之间在发病率上存在差异，表现为厌食。只有用PA+PA-Conj免疫的兔子在攻击后的观察期（14天）内始终表现正常，而所有接受含有游离荚膜肽的PA的兔子有时表现出病态，表现为不能正常进食。一只阴性对照兔子接受了较低的吸入孢子剂量（183LD50）并在攻击中存活下来，尽管它在攻击后厌食。它的恢复期血清中还具有高水平的抗LF抗体（5400 U/ml），表明感染广泛。相比之下，75%的免疫兔子在攻击后的血清中没有LF特异性抗体，其余兔子的抗体水平较低（≤138 U/ml），表明避免或大大减少了导致毒素产生的感染。因此，与单一抗原（PA）疫苗相比，用结合PA和荚膜表位的基于壳聚糖的粉末疫苗进行鼻内免疫提供了对炭疽杆菌感染的更好保护，这表现为发病率降低和预防死亡。
