The role of bacterial vaccines in the fight against antimicrobial resistance: an analysis of the preclinical and clinical development pipeline

Abstract

Vaccines can be highly effective tools in combating antimicrobial resistance as they reduce infections caused by antibiotic-resistant bacteria and antibiotic consumption associated with disease. This Review looks at vaccine candidates that are in development against pathogens on the 2017 WHO bacterial priority pathogen list, in addition to Clostridioides difficile and Mycobacterium tuberculosis. There were 94 active preclinical vaccine candidates and 61 active development vaccine candidates. We classified the included pathogens into the following four groups: Group A consists of pathogens for which vaccines already exist-ie, Salmonella enterica serotype Typhi, Streptococcus pneumoniae, Haemophilus influenzae type b, and M tuberculosis. Group B consists of pathogens with vaccines in advanced clinical development-ie, extra-intestinal pathogenic Escherichia coli, Salmonella enterica serotype Paratyphi A, Neisseria gonorrhoeae, and C difficile. Group C consists of pathogens with vaccines in early phases of clinical development-ie, enterotoxigenic E coli, Klebsiella pneumoniae, non-typhoidal Salmonella, Shigella spp, and Campylobacter spp. Finally, group D includes pathogens with either no candidates in clinical development or low development feasibility-ie, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, Helicobacter pylori, Enterococcus faecium, and Enterobacter spp. Vaccines are already important tools in reducing antimicrobial resistance and future development will provide further opportunities to optimise the use of vaccines against resistance.

Figure 1

Vaccine candidates in preclinical development, categorised by pathogen and type BPPL=bacterial priority pathogen list.

Figure 2

Vaccine candidates in active clinical development (A) Total number of vaccine candidates in active clinical development by pathogen. (B) Total number of candidates both in active clinical development and that have become inactive or discontinued over the past 10 years, by pathogen. Note that some vaccine candidates are double counted here as they target more than one pathogen. Pathogen type refers to status as defined by the WHO BPPL. BPPL=bacterial priority pathogen list.

Figure 3

Number of vaccine candidates by phase of clinical development and continued activity

Figure 4

Number of vaccine candidates in active clinical development by approach NA=not applicable. GMMA=generalised modules for membrane antigens. OMV=outer membrane vesicles.

Figure 5

Categorisation of priority pathogens as targets for vaccination Group A contains pathogens with vaccines that are already licensed. Group B contains pathogens with vaccines in late-stage clinical trials with high development feasibility. Group C contains pathogens with vaccine candidates either in early clinical trials or with moderate to high feasibility of vaccine development. Group D contains pathogens with a small number or no vaccine candidates in the pipeline and low vaccine development feasibility in the near future.