Abstract
Antimicrobial resistance (AMR) is currently the most alarming issue for human health. AMR already causes 700,000 deaths/year. It is estimated that 10 million deaths due to AMR will occur every year after 2050. This equals the number of people dying of cancer every year in present times. International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics. To underline this emergency, a list of antibiotic-resistant “priority pathogens” has been published by WHO. It contains 12 families of bacteria that represent the greatest danger for human health. Resistance to multiple antibiotics is particularly relevant for the Gram-negative bacteria present in the list. The ability of these bacteria to develop mechanisms to resist treatment could be transmitted with genetic material, allowing other bacteria to become drug resistant. Although the search for new antimicrobial drugs remains a top priority, the pipeline for new antibiotics is not promising, and alternative solutions are needed. A possible answer to AMR is vaccination. In fact, while antibiotic resistance emerges rapidly, vaccines can lead to a much longer lasting control of infections. New technologies, such as the high-throughput cloning of human B cells from convalescent or vaccinated people, allow for finding new protective antigens (Ags) that could not be identified with conventional technologies. Antibodies produced by convalescent B cell clones can be screened for their ability to bind, block, and kill bacteria, using novel high-throughput microscopy platforms that rapidly capture digital images, or by conventional technologies such as bactericidal, opsono-phagocytosis and FACS assays. Selected antibodies expressed by recombinant DNA techniques can be used for passive immunization in animal models and tested for protection. Antibodies providing the best protection can be employed to identify new Ags and then used for generating highly specific recombinant Fab fragments. Co-crystallization of Ags bound to Fab fragments will allow us to determine the structure and characteristics of new Ags. This structure-based Ag design will bring to a new generation of vaccines able to target previously elusive infections, thereby offering an effective solution to the problem of AMR.
Highlights
Specialty section: This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology
It is estimated that 10 million deaths due to Antimicrobial resistance (AMR) will occur every year after 2050. This equals the number of people dying of cancer every year in present times. International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics
On February 27th 2017, the WHO published a document5, which we partially report hereafter: “This is the first ever list of antibiotic-resistant “priority pathogens”, a catalog of 12 families of bacteria that pose the greatest threat to human health
Summary
Antibiotics are an important example of how man can learn from nature to improve his own living conditions. The second and third tiers in the list—the high and medium priority categories— include other increasingly drugresistant bacteria that cause more common diseases, such as Neisseria gonorrhoeae (the agent of gonorrhea) and Salmonella (causing food poisoning) This WHO action intends to promote initiatives of basic science and advanced R&D from both publicly funded agencies and the private sector, aiming to discover new antibiotics.”. The criteria for selecting pathogens in the list were: a) how deadly the infections they cause are; b) whether their treatment requires long hospital stays; c) how frequently they are resistant to existing antibiotics when people in communities catch them; d) how they are transmit ted between animals, from animals to humans, and from person to person; e) whether they can be prevented (e.g., through good hygiene and vaccination); f) how many treatment options remain; and g) whether new antibiotics to treat them are already in the R&D pipeline.”. Vaccines have the possibility to make a big contribution to the control of AMR
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