Oscherwitz Jon, Cease Kemp, Milich David, Braun Thomas, Yu Fen, Whitacre David
Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Veterans Administration Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA.
Toxins (Basel). 2025 Aug 20;17(8):422. doi: 10.3390/toxins17080422.
Anthrax remains a serious bioterrorism threat for which new and thermostable vaccines are needed. We previously demonstrated that immunization of rabbits with multiple-antigenic-peptide (MAP) vaccines elicit antibody (Ab) against the loop-neutralizing-determinant (LND), a cryptic linear neutralizing epitope in the 2β2-2β3 loop of protective antigen (PA) from (), which mediates the complete protection of rabbits from inhalation spore challenge with Ames strain. Importantly, LND-specific Ab is not significantly elicited with PA-based vaccines. In the current study, we sought to identify a second unique neutralizing epitope which would also not overlap with the neutralizing specificities elicited by PA-based vaccines, and which could be combined with an LND vaccine as a prototype bivalent vaccine for anthrax. We evaluated linear peptide sequences in the α2-α3 helices of domain 3 of lethal factor (LF) in the form of virus-like particle (VLP) vaccines. Immunogenicity studies confirmed the presence of a 20-mer peptide sequence that is capable of eliciting protective levels of neutralizing Ab following two immunizations of rabbits using human-use adjuvants, and lyophilization of the VLPs did not diminish their immunogenicity. To our knowledge, this is the first demonstration that immunization with linear peptide sequences from LF can elicit protective levels of neutralizing Ab in vivo.
炭疽仍然是一种严重的生物恐怖主义威胁，为此需要新型的热稳定疫苗。我们之前证明，用多抗原肽（MAP）疫苗免疫兔子可引发针对环中和决定簇（LND）的抗体（Ab），LND是来自（）的保护性抗原（PA）的2β2-2β3环中的一个隐蔽线性中和表位，它介导兔子完全抵御Ames菌株吸入孢子攻击。重要的是，基于PA的疫苗不会显著引发LND特异性抗体。在当前研究中，我们试图鉴定第二个独特的中和表位，该表位也不会与基于PA的疫苗引发的中和特异性重叠，并且可以与LND疫苗组合作为炭疽原型二价疫苗。我们以病毒样颗粒（VLP）疫苗的形式评估了致死因子（LF）结构域3的α2-α3螺旋中的线性肽序列。免疫原性研究证实存在一个20聚体肽序列，在用人类使用的佐剂对兔子进行两次免疫后，该序列能够引发具有保护水平的中和抗体，并且VLP的冻干不会降低其免疫原性。据我们所知，这是首次证明用来自LF的线性肽序列进行免疫可在体内引发具有保护水平的中和抗体。
