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 are the cornerstone of infectious disease control and prevention. The outbreak of SARS-CoV-2 has confirmed the urgent need for a new approach to the design of novel vaccines. Plant viruses and their derivatives are being used increasingly for the development of new medical and biotechnological applications, and this is reflected in a number of preclinical and clinical studies. Plant viruses have a unique combination of features (biosafety, low reactogenicity, inexpensiveness and ease of production, etc.), which determine their potential. This review presents the latest data on the use of plant viruses with different types of symmetry as vaccine components and adjuvants in cancer immunotherapy. The discussion concludes that the most promising approaches might be those that use structurally modified plant viruses (spherical particles) obtained from the Tobacco mosaic virus. These particles combine high adsorption properties (as a carrier) with strong immunogenicity, as has been confirmed using various antigens in animal models. According to current research, it is evident that plant viruses have great potential for application in the development of vaccines and in cancer immunotherapy.
This review addresses the ongoing global challenge posed by emerging and evolving viral diseases, underscoring the need for innovative vaccine development strategies. It focuses on the modern approaches to creating vaccines based on recombinant proteins produced in different expression systems, including bacteria, yeast, plants, insects, and mammals. This review analyses the advantages, limitations, and applications of these expression systems for producing vaccine antigens, as well as strategies for designing safer, more effective, and potentially ‘universal’ antigens. The review discusses the development of vaccines for a range of viral diseases, excluding SARS-CoV-2, which has already been extensively studied. The authors present these findings with the aim of contributing to ongoing research and advancing the development of antiviral vaccines.
The Newcastle disease virus (NDV), an avian paramyxovirus, induces the highly contagious Newcastle disease in poultry. Newcastle disease outbreaks, common in many developing countries, have been recorded worldwide for a century. Poultry, even vaccinated stocks, together with wild and synanthropic birds, serve as reservoirs of NDV. Despite the extensive use of commercial NDV vaccines, Newcastle disease outbreaks frequently occur in vaccinated chickens, resulting in great economic losses. The primary limitation of commercial Newcastle disease vaccines is their restricted compatibility with emerging novel NDV strains. The advancement of vaccines and vaccination techniques is anticipated to reduce the propagation of pathogenic NDV strains and consequently alleviate losses in poultry production. This review examines the NDV genotypes and strains implicated in both current and historical Newcastle disease outbreaks, and evaluates existing and candidate NDV vaccines, emphasizing recent innovations and novel techniques. Our aim was to delineate critical subjects for future inquiry and to furnish extensive data that could aid researchers in understanding the current advancements and existing problems in Newcastle disease vaccination prophylactics. The emergence of a new generation of vaccines employing advanced technologies may substantially improve the efficacy of Newcastle disease prevention and control.
Anthrax is a disease caused by Bacillus anthracis that affects mammals, including humans. Recombinant B. anthracis protective antigen (rPA) is the most common basis for modern anthrax vaccine candidates. However, this protein is characterised by low stability due to proteolysis and deamidation. Here, for the first time, two modification variants leading to full-size rPA stabilisation have been implemented simultaneously, through deamidation-prone asparagine residues substitution and by inactivation of proteolysis sites. Obtained modified rPA (rPA83m) has been demonstrated to be stable in various temperature conditions. Additionally, rPA1+2 containing PA domains I and II and rPA3+4 containing domains III and IV, including the same modifications, have been shown to be stable as well. These antigens can serve as the basis for a vaccine, since the protective properties of PA can be attributed to individual PA domains. The stability of each of three modified anthrax antigens has been considerably improved in compositions with tobacco mosaic virus-based spherical particles (SPs). rPA1+2/rPA3+4/rPA83m in compositions with SPs have maintained their antigenic specificity even after 40 days of incubation at +37 °C. Considering previously proven adjuvant properties and safety of SPs, their compositions with rPA83m/rPA1+2/rPA3+4 in any combinations might be suitable as a basis for new-generation anthrax vaccines.
2 July 2020 in Human Vaccines & Immunotherapeutics
Anthrax is a zoonotic disease caused by the gram-positive spore-forming bacteria Bacillus anthracis. There is a need for safe, highly effective, long-term storage vaccine formulations for mass vaccination. However, the development of new subunit vaccines based on recombinant protective antigen (rPA) faces the problem of vaccine antigen instability. Here, the potential of simultaneous application of two different approaches to stabilize rPA was demonstrated. Firstly, we employed spherical particles (SPs) obtained from the tobacco mosaic virus (TMV). Previously, we had reported that SPs can serve as an adjuvant and platform for antigen presentation. In the current work, SPs were shown to increase the stability of the full-size rPA without loss of its antigenic properties. The second direction was site-specific mutagenesis of asparagine residues to avoid deamidation that causes partial protein degradation. The modified recombinant protein comprising the PA immunogenic domains 3 and 4 (rPA3 + 4) was stable during storage at 4 and 25°C. rPA3 + 4 interacts with antibodies to rPA83 both individually and as a part of a complex with SPs. The results obtained can underpin the development of a recombinant vaccine with a full-size modified rPA (with similar amino acid substitutions that stabilize the protein) and SPs.