The manufacture of the UK Anthrax vaccine (AVP) focuses on Protective Antigen (PA) production from the Bacillus anthracis Sterne strain. This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using LC-MS/MS, requiring the development of a novel desorption method for releasing B. anthracis proteins from the vaccine’s aluminum-containing adjuvant. Secondly, computational MHC-binding predictions using NetMHCIIpan were made for the eight most abundant proteins of AVP, for the most common HLA alleles in multiple ethnic groups, and multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for PA and Lethal Factor (LF).

Results demonstrated that AVP is composed of at least 138 B. anthracis proteins, including PA (65%), LF (8%), and Edema Factor (EF) (3%), using LC-MS/MS. NetMHCIIpan predicted that peptides from all eight abundant proteins are likely to be presented to T cells, a protection prerequisite; however, the number of such peptides varied considerably between different HLA alleles.

These analyses highlight two essential properties of the AVP vaccine that have not been established previously. Firstly, the effectiveness of AVP within humans may not depend on PA alone; there is compelling evidence to suggest that LF has a protective role, with computational predictions suggesting that additional proteins may be necessary for individuals with specific HLA allele combinations. Secondly, despite differences in the sequences of critical antigenic proteins from different B. anthracis strains, these are unlikely to affect the cross-strain protection afforded by AVP.

Reference: https://www.tandfonline.com/doi/full/10.1080/21645515.2020.1799668

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