Vaccines against anthrax based on recombinant protective antigen: problems and solutions

ABSTRACT

Introduction: Anthrax is a dangerous bio-terror agent because Bacillus anthracis spores are highly resilient and can be easily aerosolized and disseminated. There is a threat of deliberate use of anthrax spores aerosol that could lead to serious fatal diseases outbreaks. Existing control measures against inhalation form of the disease are limited. All of this has provided an impetus to the development of new generation vaccines.

Areas сovered: This review is devoted to challenges and achievements in the design of vaccines based on the anthrax recombinant protective antigen (rPA). Scientific databases have been searched, focusing on causes of PA instability and solutions to this problem, including new approaches of rPA expression, novel rPA-based vaccines formulations as well as the simultaneous usage of PA with other anthrax antigens.

Expert opinion: PA is a central anthrax toxin component, playing a key role in the defense against encapsulated and unencapsulated strains. Subunit rPA-based vaccines have a good safety and protective profile. However, there are problems of PA instability that are greatly enhanced when using aluminum adjuvants. New adjuvant compositions, dry formulations and resistant to proteolysis and deamidation mutant PA forms can help to handle this issue. Devising a modern anthrax vaccine requires huge efforts.

KEYWORDS:

• Аdjuvant
• аnthrax
• Bacillus anthracis
• bioterrorism
• instability of PA
• protective antigen
• vaccine

Article highlights

• Anthrax is one of the most dangerous bio-terror agents. Novel safe and effective vaccines for anthrax prevention are highly needed.

• The protective antigen (PA) plays a key role in protection against encapsulated and unencapsulated strains of B. аnthracis. Full-size PA is the most promising candidate for devising vaccines.

• We have summarized information about various strategies for the production of recombinant PA (rPA), including different expression and delivery systems.

• One of the main problems in rPA-based subunit vaccine development is protein instability. There have been attempts to stabilize rPA using novel adjuvants, dry rPA formulation, and mutant protein forms resistant to degradation. These are promising ways to improve anthrax vaccine efficacy.

• Clinical trials of several full-size rPA-based vaccines are underway. Vaccine candidates are produced in different expression systems, including both wild-type rPA and proteolysis-resistant mutant forms. Clinical studies have revealed that subunit rPA-based vaccines have good safety and immunogenicity and confer protection in animal models of inhalational anthrax.

• Mucosal adjuvants or live bacterial and adenoviral delivery systems can provide a mucosal route of vaccine administration that would be important in the fight against the inhalation anthrax form.

• Developing an effective vaccine may require a combination of different strategies and heterologous prime-boost vaccination schedule.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer has disclosed that Several patents and licenses for material from their lab have in the past been licensed to vaccine makers, which has been managed by the NIH TT office. All other peer reviewers have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Russian Science Foundation [Grant no.18-14-00044].