Dumas Eric K, Garman Lori, Cuthbertson Hannah, Charlton Sue, Hallis Bassam, Engler Renata J M, Choudhari Shyamal, Picking William D, James Judith A, Farris A Darise
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation (OMRF), 825 NE 13th St., Oklahoma City, OK 73104, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC), 940 Stanton L. Young Blvd, Oklahoma City, OK 73104, USA.
Public Health England, National Infection Service, Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom.
Vaccine. 2017 Jun 8;35(26):3416-3422. doi: 10.1016/j.vaccine.2017.05.006. Epub 2017 May 11.
A major difference between two currently licensed anthrax vaccines is presence (United Kingdom Anthrax Vaccine Precipitated, AVP) or absence (United States Anthrax Vaccine Adsorbed, AVA) of quantifiable amounts of the Lethal Toxin (LT) component Lethal Factor (LF). The primary immunogen in both vaccine formulations is Protective Antigen (PA), and LT-neutralizing antibodies directed to PA are an accepted correlate of vaccine efficacy; however, vaccination studies in animal models have demonstrated that LF antibodies can be protective. In this report we compared humoral immune responses in cohorts of AVP (n=39) and AVA recipients (n=78) matched 1:2 for number of vaccinations and time post-vaccination, and evaluated whether the LF response contributes to LT neutralization in human recipients of AVP. PA response rates (≥95%) and PA IgG concentrations were similar in both groups; however, AVP recipients exhibited higher LT neutralization ED values (AVP: 1464.0±214.7, AVA: 544.9±83.2, p<0.0001) and had higher rates of LF IgG positivity (95%) compared to matched AVA vaccinees (1%). Multiple regression analysis revealed that LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group. Affinity purified LF antibodies from two independent AVP recipients neutralized LT and bound to LF Domain 1, confirming contribution of LF antibodies to LT neutralization. This study documents the benefit of including an LF component to PA-based anthrax vaccines.
目前两种已获许可的炭疽疫苗之间的一个主要区别在于是否存在可量化的致死毒素（LT）成分致死因子（LF）（英国沉淀炭疽疫苗，AVP）或不存在（美国吸附炭疽疫苗，AVA）。两种疫苗制剂中的主要免疫原都是保护性抗原（PA），针对PA的LT中和抗体是公认的疫苗效力相关指标；然而，动物模型中的疫苗接种研究表明，LF抗体也具有保护作用。在本报告中，我们比较了接种次数和接种后时间1:2匹配的AVP队列（n = 39）和AVA接种者（n = 78）的体液免疫反应，并评估了LF反应是否有助于AVP人类接种者的LT中和。两组的PA反应率（≥95%）和PA IgG浓度相似；然而，与匹配的AVA疫苗接种者（1%）相比，AVP接种者表现出更高的LT中和ED值（AVP：1464.0±214.7，AVA：544.9±83.2，p<0.0001），且LF IgG阳性率更高（95%）。多元回归分析显示，LF IgG对AVP组中的LT中和反应有独立的累加贡献。来自两名独立AVP接种者的亲和纯化LF抗体中和了LT并与LF结构域1结合，证实了LF抗体对LT中和的作用。本研究证明了在基于PA的炭疽疫苗中加入LF成分的益处。
