CpG Oligonucleotides (ODN) are immunomodulatory synthetic oligonucleotides specifically designed to stimulate Toll-like receptor 9. TLR9 is expressed on human plasmacytoid dendritic cells and B cells and triggers an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. This chapter reviews recent progress in understanding the mechanism of action of CpG ODN and provides an overview of human clinical trial results using CpG ODN to improve vaccines for the prevention/treatment of cancer, allergy, and infectious disease.

CpG Oligonucleotides as Vaccine Adjuvants.

Bacillus anthracis has been identified as a potential military and bioterror agent as it is relatively simple to produce, with spores that are highly resilient to degradation in the environment and easily dispersed. These characteristics are important in describing how anthrax could be used as a weapon, but they are also important in understanding and determining appropriate prevention and treatment of anthrax disease. Today, anthrax disease is primarily enzootic and found mostly in the developing world, where it is still associated with considerable mortality and morbidity in humans and livestock. This review article describes the spectrum of disease caused by anthrax and the various prevention and treatment options. Specifically we discuss the following; (1) clinical manifestations of anthrax disease (cutaneous, gastrointestinal, inhalational and intravenous-associated); (2) immunology of the disease; (3) an overview of animal models used in research; (4) the current World Health Organization and U.S. Government guidelines for investigation, management, and prophylaxis; (5) unique regulatory approaches to licensure and approval of anthrax medical countermeasures; (6) the history of vaccination and pre-exposure prophylaxis; (7) post-exposure prophylaxis and disease management; (8) treatment of symptomatic disease through the use of antibiotics and hyperimmune or monoclonal antibody-based antitoxin therapies; and (9) the current landscape of next-generation product candidates under development.

Current Status and Trends in Prophylaxis and Management of Anthrax Disease.

Introduction: Anthrax is a dangerous bio-terror agent because Bacillus anthracis spores are highly resilient and can be easily aerosolized and disseminated. There is a threat of deliberate use of anthrax spores aerosol that could lead to serious fatal diseases outbreaks. Existing control measures against inhalation form of the disease are limited. All of this has provided an impetus to the development of new generation vaccines. Areas сovered: This review is devoted to challenges and achievements in the design of vaccines based on the anthrax recombinant protective antigen (rPA). Scientific databases have been searched, focusing on causes of PA instability and solutions to this problem, including new approaches of rPA expression, novel rPA-based vaccines formulations as well as the simultaneous usage of PA with other anthrax antigens. Expert opinion: PA is a central anthrax toxin component, playing a key role in the defense against encapsulated and unencapsulated strains. Subunit rPA-based vaccines have a good safety and protective profile. However, there are problems of PA instability that are greatly enhanced when using aluminum adjuvants. New adjuvant compositions, dry formulations and resistant to proteolysis and deamidation mutant PA forms can help to handle this issue. Devising a modern anthrax vaccine requires huge efforts.

Vaccines against anthrax based on recombinant protective antigen: problems and solutions.

Sepsis involves a disordered host response to systemic infection leading to high morbidity and mortality. Despite intense research, targeted sepsis therapies beyond antibiotics have remained elusive. The cornerstone of sepsis research is the development of animal models to mimic human bacterial infections and test novel pharmacologic targets. Nonhuman primates (NHPs) have served as an attractive, but expensive, animal to model human bacterial infections due to their nearly identical cardiopulmonary anatomy and physiology, as well as host response to infection. Several NHP species have provided substantial insight into sepsis-mediated inflammation, endothelial dysfunction, acute lung injury, and multi-organ failure. The use of NHPs has usually focused on translating therapies from early preclinical models to human clinical trials. However, despite successful sepsis interventions in NHP models, there are still no FDA-approved sepsis therapies. This review highlights major NHP models of bacterial sepsis and their relevance to clinical medicine. Treatment for bacterial sepsis remains limited beyond the use of antibiotics. Lingye Chen, Karen Welty-Wolf, and Bryan Kraft review nonhuman primate models of sepsis and highlight their advantages and limitations compared to other preclinical models.

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Nonhuman primate species as models of human bacterial sepsis

A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.

https://www.mdpi.com/2076-2607/8/5/651/pdf

Current State of Anthrax Vaccines and Key R&D Gaps Moving Forward

Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate.

Na Li

Papers

Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate.

Efficacy of the AV7909 anthrax vaccine candidate in guinea pigs and nonhuman primates following two immunizations two weeks apart.