COMPARATIVE EFFICACY OF EXPERIMENTAL ANTHRAX VACCINE CANDIDATES AGAINST INHALATION ANTHRAX IN RHESUS MACAQUES

The authors examined the efficacy of Bacillus anthracis protective ant igen (PA) combined with adjuvants as vaccines against an aerosol chall enge of virulent anthrax spores in rhesus macaques. Adjuvants tested i ncluded i) aluminum hydroxide (Alhydrogel), ii) saponin QS-21 and iii) monophosphoryl lipid A (MPL) in squalene/lecithin/Tween 80 emulsion ( SLT). Animals were immunized once with either 50 mu g of recombinant P A plus adjuvant, or with Anthrax Vaccine Adsorbed (AVA), the licensed human anthrax vaccine. The serological response to PA was measured by enzyme-linked immunosorbent assay. Lymphocyte proliferation and serum neutralization of in vitro lethal toxin cytotoxicity were also assayed . In all vaccine groups, anti-PA IgM and IgG titers peaked at 2 weeks and 4-5 weeks postimmunization, respectively. Five weeks postimmunizat ion, animals in all vaccine groups demonstrated PA-specific lymphocyte proliferation and sera that neutralized in vitro cytotoxicity. Six we eks after immunization, the animals were challenged by aerosol with ap proximately 93 LD50 of virulent anthrax spores. Animals were bled dail y for 1 week to monitor bacteremia, and deaths were recorded. Anti-PA ELISA titers in all groups of immunized animals were substantially inc reased 2 weeks after challenge. One dose of each vaccine provided sign ificant protection (> 90%) against inhalation anthrax in the rhesus ma caques. Published by Elsevier Science Ltd.