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Vaccine Development
Published in Joseph R. Masci, Elizabeth Bass, Ebola, 2017
Joseph R. Masci, Elizabeth Bass
Two primates, the rhesus and the cynomolgus monkey, had been established as the usual animal models for research into Ebola virus vaccines. Another primate, the macaque monkey, when infected develops a disease most similar to Ebola virus disease (EVD) seen in humans. A number of rodent models also have been used in vaccine trials to establish immunogenicity of various vaccine preparations. Because of the difficulty in conducting human trials of vaccines against sporadic and highly lethal conditions like EVD, the United States Food and Drug Administration (FDA) has asserted the so-called animal rule for the development and approval of such vaccines. This rule permits licensing of vaccines if they have been demonstrated to be safe and effective in appropriate animal models. It was applied by the FDA for the first time in 2015, when it licensed the anthrax vaccine BioThrax (Beasley et al. 2016).
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
Aluminum hydroxide (alum) is one adjuvant that is widely used with subunit vaccines. One example of a current clinical subunit vaccine that includes alum is the anthrax vaccine adsorbed (AVA) which is produced under the name BioThrax® (Emergent BioDefense Corporation) and first licensed for human use in 1970 [25]. AVA contains the anthrax protective antigen (PA) protein and is adjuvanted with alum. Alum containing adjuvants were first found to be immunostimulatory in 1926 and since then they have been used in various vaccines such as diphtheria, pertussis, and tetanus [26]. Broadly, alum covers multiple similar adjuvants and can include aluminum salts such as aluminum hydroxide, aluminum phosphate, and aluminum potassium sulfate. Although the exact mechanism of alum is still in contention, it is thought that these adjuvants promote immunogenicity by adsorbing antigens as well as causing local inflammation at the site of injection resulting in activation of the NLR family pyrin domain containing 3 (NLR3) inflammasome [27,28]. This in turn promotes a strong Th2 response with high levels of neutralizing antibodies; however, alum only very weakly activates a Th1 response. Furthermore, while AVA is effective in producing neutralizing antibodies against PA the protection is extremely inefficient requiring 5 doses followed by boosters every 12–18 months [29].
Vaccines against anthrax based on recombinant protective antigen: problems and solutions
Published in Expert Review of Vaccines, 2019
Olga A. Kondakova, Nikolai A. Nikitin, Ekaterina A. Evtushenko, Ekaterina M. Ryabchevskaya, Joseph G. Atabekov, Olga V. Karpova
Live attenuated vaccines are used in Russia (live spores from the attenuated strain STI-1 of B. anthracis) and China (а suspension of the attenuated strain A16R of B.anthracis). Results of live anthrax vaccine trials are described in detail in [14–16]. Both these vaccines provide good protection; however, they are not used for human protection in the West. Two licensed subunit PA-based human vaccines – anthrax vaccine adsorbed (AVA, BioThrax™) in the US and anthrax vaccine precipitated (AVP) in the UK – have been used to vaccinate humans for more than 40 years. Both vaccines are obtained by generating attenuated (pXO1+/pXO2-) B. аnthracis strains V770-NP1-R (AVA) and Sterne 34F2 (AVP) in liquid cultures, further using a cell-free filtrate as the basis for the vaccine. In AVA, as well as in AVP, the protective antigen of B. anthracis serves as a major immunogen [17,18]. Due to technological issues, both vaccines inevitably contain some traces of LF and EF, which may cause adverse reactions. AVA contains unquantified amounts of PA and small quantities of LF and EF. AVA-induced antibodies to LF and EF were demonstrated not to influence neutralization of the anthrax toxin [19–21]. In contrast to AVA, AVP contains PA in the concentration of 7.9 μg/mL, LF – 1.9 μg/mL and detectable amounts of EF. AVP-induced antibodies to EF also have no effect on anthrax toxin neutralization [20]. However, anti-LF IgG makes an independent and additive contribution to the LT neutralization response in the AVP group [21]. Other differences between the vaccines include adsorption to aluminum hydroxide gel (AVA) versus precipitation with aluminum potassium sulfate (AVP) and the use of different preservatives [22,23].