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

2020 ◽  
Vol 113 (1) ◽  
pp. 32-42
Author(s):  
Eve Mylchreest ◽  
M. Autumn Smiley ◽  
Jeff D. Ballin ◽  
Bruna Blauth ◽  
Jeffry Shearer ◽  
...  
2009 ◽  
Vol 81 (10) ◽  
pp. 1777-1785 ◽  
Author(s):  
Natalia S. Pripuzova ◽  
Natalia V. Tereshkina ◽  
Larissa V. Gmyl ◽  
Tatiana I. Dzhivanyan ◽  
Alexander A. Rumyantsev ◽  
...  

Vaccine ◽  
2017 ◽  
Vol 35 (41) ◽  
pp. 5463-5470 ◽  
Author(s):  
R. Mark Jones ◽  
Michael Burke ◽  
Devon Dubose ◽  
Jessica A. Chichester ◽  
Slobodanka Manceva ◽  
...  

2020 ◽  
Vol 39 (5) ◽  
pp. 443-451
Author(s):  
Amy Zmarowski ◽  
Jeff D. Ballin ◽  
Jessica Sharits ◽  
Kevin Carrico ◽  
Joseph Novak ◽  
...  

AV7909 is a next-generation anthrax vaccine candidate indicated for post-exposure prophylaxis of exposure to Bacillus anthracis. AV7909 consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and the immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant, CPG 7909. Safety testing for pediatric population is warranted to support the potential emergency use of AV7909 in children. This study was conducted to investigate the local tolerance and potential systemic toxicity and their reversibility in juvenile rats by repeat intramuscular injections of the AV7909 vaccine candidate. Animals were dosed on postnatal day (PND) 21 (at weaning), PND 28, and PND 35, with the test article (AV7909), the adjuvant alone (Alhydrogel + CPG 7909), or sterile water for injection. Core group animals were necropsied on PND 37 and recovery group on PND 49. Study end points included survival, clinical observations, injection site observations, body weights, clinical pathology (hematology, coagulation, and clinical chemistry), pro-inflammatory biomarker analysis (alpha-2 macroglobulin [A2M] and alpha-1 acid glycoprotein [AGP]), and anatomic pathology. Immune response to vaccination was measured using the high-throughput anthrax lethal toxin neutralization assay (htpTNA). The AV7909 vaccine candidate produced no apparent systemic or local toxicity. The AGP and A2M levels were elevated in both the adjuvant-alone and AV7909 groups at the end of treatment but were comparable to control levels by the end of the recovery period. All animals in the AV7909 group demonstrated a robust neutralizing antibody response. The results indicate that AV7909 has a favorable safety profile in juvenile rats.


Vaccine ◽  
2021 ◽  
Vol 39 (1) ◽  
pp. 1-5
Author(s):  
Jeffry D. Shearer ◽  
Lisa Henning ◽  
Daniel C. Sanford ◽  
Na Li ◽  
Mario H. Skiadopoulos ◽  
...  

Vaccine ◽  
2017 ◽  
Vol 35 (37) ◽  
pp. 4952-4959 ◽  
Author(s):  
Vladimir Savransky ◽  
Jeffry D. Shearer ◽  
Melicia R. Gainey ◽  
Daniel C. Sanford ◽  
Gloria S. Sivko ◽  
...  

Vaccine ◽  
2019 ◽  
Vol 37 (43) ◽  
pp. 6356-6361 ◽  
Author(s):  
M. Autumn Smiley ◽  
Daniel C. Sanford ◽  
Cheryl A. Triplett ◽  
Daniel Callahan ◽  
Vladimir Frolov ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jun Ho Jeon ◽  
Yeon Hee Kim ◽  
Kyung Ae Kim ◽  
Yu-Ri Kim ◽  
Sun-Je Woo ◽  
...  

Abstract Background Bacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions. Methods We selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model. Results The recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model. Conclusions Our results suggest that r0190 may be a potential target for anthrax vaccine.


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