Single dose of DPX-rPA, an enhanced-delivery anthrax vaccine formulation, protects against a lethal Bacillusanthracis spore inhalation challenge

Genevieve M Weir,Leeladhar Sammatur,Bradley J Berger,Rajkannan Rajagopalan,Michelle W Valderas,Marianne M Stanford,Gloria S Sivko,Jonathan Rayner,Lisa D Macdonald

doi:10.1038/s41541-019-0102-z

Genevieve M Weir, Leeladhar Sammatur + Show 7 more

Open Access

https://doi.org/10.1038/s41541-019-0102-z

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Abstract

Anthrax is a serious biological threat caused by pulmonary exposure to aerosolized spores of Bacillus anthracis. Biothrax® (anthrax vaccine adsorbed (AVA)) is the only Food and Drug Administration-licensed vaccine and requires five administrations over 12 months with annual boosting to maintain pre-exposure prophylaxis. Here we report the evaluation of a single intramuscular injection of recombinant B. anthracis-protective antigen (rPA) formulated in the DPX delivery platform. Immune responses were compared to an alum-based formulation in mice and rabbits. Serological analysis of anti-rPA immunoglobulin G and toxin neutralization activity demonstrated higher responses induced by DPX-rPA when compared to rPA in alum. DPX-rPA was compared to AVA in rabbits and non-human primates (NHPs). In both species, DPX-rPA generated responses after a single immunization, whereas AVA required two immunizations. In rabbits, single injection of DPX-rPA or two injections of AVA conferred 100% protection from anthrax challenge. In NHPs, single-dose DPX-rPA was 100% protective against challenge, whereas one animal in the two-dose AVA group and all saline administered animals succumbed to infection. DPX-rPA was minimally reactogenic in all species tested. These data indicate that DPX-rPA may offer improvement over AVA by reducing the doses needed for protective immune responses and is a promising candidate as a new-generation anthrax vaccine.

Highlights

Anthrax is a rapid-onset disease considered a serious biological warfare threat
The predominant means of protection provided by anthrax vaccine adsorbed (AVA) is thought to be mediated by antibodies generated against protective antigen (PA), interfering with PA-mediated cellular entry of the anthrax toxins lethal factor (LF) and edema factor (EF).[5]
The results demonstrate the ability of DPX-recombinant B. anthracis-protective antigen (rPA) to generate functional antirPA immunoglobulin G (IgG) in serum and to confer protection from aerosolized lethal B. anthracis spore challenge in multiple species

Summary

Introduction

Anthrax is a rapid-onset disease considered a serious biological warfare threat. Anthrax is caused by Bacillus anthracis (B. anthracis), a spore-forming Gram-positive bacterium that can be transmitted by gastrointestinal, cutaneous, or inhalation exposure routes. While AVA is considered safe and efficacious, the pre-exposure vaccination regimen consists of three priming doses at 0, 1, and 6 months, with booster doses given at 6 and 12 months after completion of the priming series and annually thereafter. This regimen is not favorable to immunization of the general population and may contribute to injection site issues such as subcutaneous nodules, erythema, and induration.[6] recently approved for a post-exposure setting, the US Centers for Disease Control and Prevention (CDC) recommends at least 5 weeks of continuous antibiotic treatment in parallel with vaccination, which is challenging for widespread deployment. Due to concerns with the protracted dosing regimen and reactogenicity of AVA, alternative vaccine options that require fewer injections to promote rapid, enhanced protective immunity are currently under investigation for both pre-exposure and post-exposure prophylaxis measures

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