Quinn Conrad P, Sabourin Carol L, Niemuth Nancy A, Li Han, Semenova Vera A, Rudge Thomas L, Mayfield Heather J, Schiffer Jarad, Mittler Robert S, Ibegbu Chris C, Wrammert Jens, Ahmed Rafi, Brys April M, Hunt Robert E, Levesque Denyse, Estep James E, Barnewall Roy E, Robinson David M, Plikaytis Brian D, Marano Nina
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clin Vaccine Immunol. 2012 Nov;19(11):1730-45. doi: 10.1128/CVI.00324-12. Epub 2012 Aug 29.
A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA or following two injections of diluted vaccine (1:10, 1:20, or 1:40 AVA). Anti-PA and TNA were highly correlated (overall r(2) = 0.89 for log(10)-transformed data). Peak responses were seen at 6.5 months. In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 1:20 AVA), and through 50.5 months for the HuAVA and 1:5 and 1:10 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4(+) cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.
在恒河猴中，人用剂量（HuAVA）以及炭疽疫苗吸附剂（AVA）高达1:10稀释度的3剂（0、1和6个月）肌肉注射（3-IM）初免系列，提供了长达4年的针对吸入性炭疽的具有统计学意义的保护水平（60%至100%）。单次注射HuAVA或1:5 AVA后，或两次注射稀释疫苗（1:10、1:20或1:40 AVA）后，可检测到血清抗保护性抗原（抗-PA）IgG和致死毒素中和活性（TNA）。抗-PA和TNA高度相关（对数转换数据的总体r² = 0.89）。在6.5个月时出现峰值反应。一般来说，除了接受1:40 AVA的动物外，血清抗-PA和TNA反应在28.5个月（1:20 AVA测量的最后时间点）时仍显著高于对照水平，对于HuAVA以及1:5和1:10 AVA组，在50.5个月时也是如此（P < 0.05）。PA特异性γ干扰素（IFN-γ）和白细胞介素-4（IL-4）CD4⁺细胞频率以及T细胞刺激指数在50.5个月（测量的最后时间点）时持续存在。PA特异性记忆B细胞频率变化很大，但一般在2个月时可在外周血单核细胞（PBMC）中检测到，在7个月时显著高于对照水平，并且在HuAVA以及1:5和1:20 AVA组中，直到42个月（测量的最后时间点）仍可检测到。HuAVA和稀释的AVA引发了Th1/Th2联合反应和强大的免疫初免，持续产生高亲和力的PA特异性功能性抗体、长期免疫细胞活性以及免疫记忆（1:20 AVA为30个月，1:10 AVA为52个月）。在吸入性炭疽中存活的接种动物产生了高强度的回忆性抗-PA IgG和TNA反应。
