Characterization of the UK anthrax vaccine and human immunogenicity

Abstract

The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Bacillus anthracis Sterne strain. Although used for decades, several of AVP's fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and whether the degree of protection varies between individuals. This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using liquid chromatography tandem mass-spectrometry (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 commonest HLA alleles in multiple ethnic groups, and for multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for both PA and Lethal Factor (LF). It was 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 prerequisite for protection; however, the number of such peptides varied considerably between different HLA alleles. These analyses highlight two important 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 important for individuals with specific HLA allele combinations. Secondly, in spite of differences in the sequences of key antigenic proteins from different B. anthracis strains, these are unlikely to affect the cross-strain protection afforded by AVP.

Bibliometric Analysis and Visualization Mapping of Anthrax Vaccine Publications from 1991 through 2021

“…Bacillus anthracis is an extremely virulent bacterium whose spores can survive for long periods in the environment, are easily transmitted, and are linked to high morbidity and mortality rates. As a result of these factors, anthrax has received increased consideration as a prospective agent for bioterrorism and warfare; the authorities are concerned with building up stocks of anthrax vaccines to protect public health by employing mass immunization if needed [ 15 , 16 ].…”

Overcoming challenges of improving legacy biopharmaceutical processes

“…Therefore, a set of new analytical methods such as ELISA, mass spectrometry (MS), Western blot, SDS‐PAGE and two‐dimensional gel electrophoresis were developed to characterise the vaccine manufacturing process (Table 1). 60–62 These methods were used to analyse in‐process samples from both the cell culture process using a single‐use bioreactor and the current vaccine manufacturing process, and helped to demonstrate that the product from the improved process using the single‐use bioreactor was equivalent to the current process in terms of product identity and quality. An example of a two‐dimensional gel electrophoresis characterisation image of AVP is shown in Fig.…”

Secretory System Components as Potential Prophylactic Targets for Bacterial Pathogens

“…There are 2 vaccines available commercially against the pathogen: the acellular Anthrax Vaccine Precipitated (AVP) consisting of alum-precipitated B. anthracis Sterne strain crude culture filtrates [38] and the Anthrax Vaccine Adsorbed (AVA) aluminum hydroxideadsorbed product consisting mainly of PA from the B. anthracis strain V770-NP1-R. Both vaccines have to be given intramuscularly and the injection repeated after a year to maintain their effectiveness.…”