Vaccines Against Antimicrobial Resistance

Abstract

In the last century, life expectancy has increased considerably, thanks to the introduction of antibiotics, hygiene and vaccines that have contributed to the cure and prevention of many infectious diseases. The era of antimicrobial therapy started in the nineteenth century with the identification of chemical compounds with antimicrobial properties. However, immediately after the introduction of these novel drugs, microorganisms started to become resistant through different strategies. Although resistance mechanisms were already present before antibiotic introduction, their large-scale use and mis-use have increased the number of resistant microorganisms. Rapid spreading of mobile elements by horizontal gene transfer such as plasmids and integrative conjugative elements (ICE) carrying multiple resistance genes has dramatically increased the worldwide prevalence of relevant multi drug-resistant human pathogens such as Staphylococcus aureus, Neisseria gonorrhoeae, and Enterobacteriaceae. Today, antimicrobial resistance (AMR) remains one of the major global concerns to be addressed and only global efforts could help in finding a solution. In terms of magnitude the economic impact of AMR is estimated to be comparable to that of climate global change in 2030. Although antibiotics continue to be essential to treat such infections, non-antibiotic therapies will play an important role in limiting the increase of antibiotic resistant microorganisms. Among non-antibiotic strategies, vaccines and therapeutic monoclonal antibodies (mAbs) play a strategic role. In this review, we will summarize the evolution and the mechanisms of antibiotic resistance, and the impact of AMR on life expectancy and economics.

Keywords: antimicrobial resistance (AMR); infectious diseases; mechanisms of antibiotic resistance; vaccine development; vaccines; vaccinology.

Figure 1

Life expectancy increase along human civilization. In the last century, life expectancy has increased considerably, thanks to the introduction of hygiene, clean water, antibiotics, and vaccines as a means of treatment and prevention of many infectious diseases.

Figure 2

Number of deaths and the main causes (Left) in 2019 and the projection of number of deaths due to AMR infections in 2050 (in red in the Right). Gray areas represent other causes of deaths.

Figure 3

Schematic representation of the main mechanisms exploited by bacteria to tackle the action of antibiotics. (A) The inactivation of the drug by its hydrolysis or structural modification. (B) The prevention of the access to the target by reducing membrane permeability or overexpression of efflux pumps. (C) Changes in the antibiotic targets by mutation or post-translational modifications. (D) Resistance mechanism of Mycobacterium tuberculosis to isoniazid drug mutations in the katG gene causes the accumulation of the inactive form of the antibiotic inside the bacilli without the formation of active adduct.

Figure 4

Evolution of vaccine technologies and platforms. MenACWY, meningococcus ACWY; Pneumo, pneumococcus; HBV, hepatitis B virus; Hib, type B Haemophilus influenzae; GBS, group B Streptococcus, GAS HPV, human papillomavirus; MenB, meningococcus B; GAS, group A streptococcus; ExPEC, extraintestinal pathogenic E. coli; Generalized Modules for Membrane Antigens, GMMA.