Reproductive toxicity of BioThrax^® in rabbits

Abstract

AVA directly, or indirectly through the production of anti-PA IgG, did not appear to have an adverse effect on the pregnant females or their offspring, as measured by mating and fertility indices, natural delivery observations, clinical signs, gross lesions, in utero growth and survival, morphological development, or kit viability.

Repeat Dose Toxicity Study of the AV7909 Anthrax Vaccine Candidate in Juvenile Rats

“…Sponsors are ultimately left to design fit-forpurpose juvenile animal studies on a case-by-case basis. 10,19,20 In the case of the present study, it was modeled on a repeatdose toxicity study in adult animals but evaluated potential toxicity in a juvenile population. 21 The adjuvant-alone and AV7909 vaccine candidate were both well tolerated, and all animals in the AV7909 group mounted a robust immune response at PND 37 and PND 49.…”

“…Presently, safety data on AV7909 in the juvenile population are limited, although the AVA component of the vaccine candidate was evaluated in a developmental and reproductive toxicity study in rabbits where AVA vaccination of dams (twice prior to mating and once during gestation) produced anti-PA immunoglobulin G antibodies that were transferred to their offspring in utero. 10 While a robust immune activation was observed in dams, fetuses and kits, no adverse effects were observed. 10 The available safety data in adult animals and humans suggest that AV7909 has a good safety profile and is well tolerated.…”

“…10 While a robust immune activation was observed in dams, fetuses and kits, no adverse effects were observed. 10 The available safety data in adult animals and humans suggest that AV7909 has a good safety profile and is well tolerated. In the absence of an immediate threat of anthrax exposure, it would not be feasible to conduct a clinical study to evaluate the safety of AV7909 in pediatric populations.…”

Developmental and reproductive safety evaluation of AV7909 anthrax vaccine candidate in rats

“…Vaccination with rPA7909, a recombinant protective antigen anthrax vaccine candidate adjuvanted with CPG 7909, produced robust immune activation in adult rodents with no systemic toxicity observed after the full human dose of vaccine was administered (Savransky, Lacy, Ionin, Skiadopoulos, & Shearer, 2019). BioThrax vaccination of female rabbits twice prior to mating and once during gestation did not produce any reproductive or developmental toxicity while generating a robust immune response and antibody transfer to fetuses and pups (Franco, Lewis, Morseth, Simon, & Waytes, 2009). According to an analysis, inadvertent anthrax vaccination during pregnancy did not find significant associations between vaccination with BioThrax during pregnancy and birth defects risk in female military service members (Conlin, Sevick, Gumbs, Khodr, & Bukowinski, 2017).…”

Health-related quality of life in the CDC Anthrax Vaccine Adsorbed Human Clinical Trial

“…Licensed in 1970 to be administered at 0, 2, and 4 weeks and 6, 12, and 18 months, followed by annual boosters, Anthrax Vaccine Adsorbed (AVA, BioThrax ® , Emergent BioSolutions, Lansing, MI [1]) is the only anthrax vaccine licensed in the U.S., and the only U.S. licensed aluminum-adjuvant vaccine administered subcutaneously. Despite evidence supporting the vaccine being reasonably safe [2], concerns have been expressed regarding various adverse effects of AVA, including high rates of local adverse events [3,4], potential reproductive toxicity [5,6] and nonspecific longer-term symptoms such as Gulf War and chronic fatigue syndromes [7,8].…”