The role of vaccines in combatting antimicrobial resistance

Abstract

The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.

Fig. 1. Effects of vaccines on antimicrobial resistance.

a | Antimicrobial-resistant bacterial pathogens can cause serious, potentially life-threatening infections in individuals. Treatment with currently available first-line antibiotics is ineffective against resistant infections, and second-line antibiotics may be required to resolve the infection. However, use of the second-line antibiotic may promote the emergence of new antimicrobial-resistant isolates resistant to second-line antibiotics. At the population level, the emergence and spread of antimicrobial resistance (AMR) consequently leads to difficulties in treating patients who are infected. Pathogens resistant to antimicrobials cause substantial morbidity and death. b | Vaccines against antimicrobial-resistant pathogens could prevent or reduce life-threatening diseases and thus decrease health care costs, and also reduce the use of antibiotics (both first-line and second line drugs) with the potential of decreasing the emergence of AMR. If sufficient vaccine coverage is achieved in a population, indirect protection (herd immunity) further prevents spread of resistant strains. Decreased disease burden would also negate the need for antibiotics.

Fig. 2. Mechanisms of action of antibiotics and vaccines and emergence of resistance.

Antibiotics, which are most commonly administered therapeutically, act on established infections against many bacteria, increasing the probability that resistant clones emerge. Antibiotics usually have a single mechanism of action; that is, a single target, such as the bacterial cell wall or the translation machinery. Bacteria either are intrinsically resistant or acquire and/or develop antibiotic resistance (resistance mechanisms include preventing access to antibiotic targets, drug efflux, changes in the drug targets and modification or inactivation of the antibiotic itself). Thus, for example, changes in the drug target by a single mutation render the antibiotic ineffective. In addition, selective pressure exerted by antibiotics favours the emergence of resistant clones. Vaccines, by acting in a preventive manner, decrease the probability that resistant clones are selected. Vaccines often target multiple antigens and/or multiple epitopes of the same antigen (polyclonal antibodies), and thus the emergence of vaccine escape variants would require several mutations impacting different epitopes. However, it is possible that resistant clones emerge through mutations or by serotype replacement.

Fig. 3. Vaccine development for antimicrobial-resistant pathogens.

Shown are vaccine candidates that are currently at different stages of development. Various vaccine technologies and platforms (protein vaccine, glycoconjugate, synthetic conjugate, bioconjugate, outer membrane vesicles (OMVs) and live attenuated vaccines) are being applied to identify and develop such vaccines, as indicated. (see also Supplementary Table 1). ExPEC, extraintestinal pathogenic Escherichia coli; GAS, group A Streptococcus; iNTS, invasive non-typhoidal Salmonella.