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

Autor: Gloria S. Sivko, Lisa MacDonald, Marianne M. Stanford, Michelle Wright Valderas, Leeladhar Sammatur, Jon O. Rayner, Bradley J. Berger, Genevieve Weir, Rajkannan Rajagopalan
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: npj Vaccines, Vol 4, Iss 1, Pp 1-9 (2019)
NPJ Vaccines
ISSN: 2059-0105
Popis: 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.
Anthrax: Rapid immunity to a biological threat A lipid-based anthrax vaccine formulation offers immunity from the first injection. Bacillus anthracis is a lethal pathogen at high risk for use in biological warfare. The only FDA-licensed vaccine for anthrax, AVA, requires multiple doses over six months followed by regular boosters, indicating a need for rapidly immunizing vaccines. Genevieve Weir and Lisa MacDonald, from IMV Inc., with Canadian and US collaborators, here describe a prophylactic consisting of B. anthracis antigens suspended in a lipid-in-oil formulation. Their candidate, DPX-rPA, generated antigen-specific antibodies in rabbits and monkeys after one dose, compared to two for AVA. DPX-rPA also protected both species from B. anthracis spores after one dose. The results indicate that single-dose DPX-rPA is equally protective as two doses of AVA and could serve as pre-exposure and post-exposure prophylaxis. Future studies may confirm its potential as a vaccine for humans.
Databáze: OpenAIRE
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