Fighting AMR with vaccines

As the World Health Organisation has recently claimed that Antimicrobial Resistance (AMR) is one of the top 10 public health threats facing humanity, Health Business examines their recent report into vaccination to fight AMR

Recent statistics from the World Health Organisation (WHO) show that resistant bacterial infections are associated with around five million deaths a year, with more than 1.2 million deaths directly attributed to it, causing the WHO to dub AMR the “silent pandemic”.
    
Releasing its first ever report on the pipeline of vaccines to tackle antimicrobial resistant (AMR) bacterial pathogens, the WHO calls for an acceleration of trials for AMR-related vaccines in late-stage development.
    
AMR occurs when bacteria, viruses, fungi and parasites change over time and do not respond to medicines. This makes infections harder to treat and increases the risk of disease spreading, as well as severe illness and even death.

Infection Prevention
The report focuses on preventing infections using vaccination. This would then reduce the use of antibiotics, which is one of the main drivers of AMR. Currently only one of the top six bacterial pathogens responsible for deaths due to AMR - pneumococcal disease - has a vaccine. With a focus on vaccines as a tool to prevent infections from occurring in the first place, the report tries to push investment and research into feasible vaccines to combat AMR.
    
There are 61 potential vaccine candidates in various stages of clinical development, according to the report, with several in the late stages of development to fight diseases on the bacterial priority pathogens list.
    
This list includes under Priority 1: CRITICAL:  Acinetobacter baumannii, carbapenem-resistant; Pseudomonas aeruginosa, carbapenem-resistant; and Enterobacteriaceae, carbapenem-resistant, ESBL-producing. Under Priority 2: HIGH, this list includes: Enterococcus faecium, vancomycin-resistant; Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant; Helicobacter pylori; clarithromycin-resistant; Campylobacter spp., fluoroquinolone-resistant; Salmonellae, fluoroquinolone-resistant and Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant.  There are three priority pathogens listed under Priority 3: MEDIUM: Streptococcus pneumoniae, penicillin-non-susceptible; Haemophilus influenzae, ampicillin-resistant and Shigella spp., fluoroquinolone-resistant.

The report says that these late-stage vaccines have a high development feasibility, but warns that they are unlikely to be available anytime soon.

Equitable access
The WHO has called for global and equitable access to the vaccines that already exist, especially among those that need them in limited-resource settings. Vaccines already exist for four priority bacterial pathogens: pneumococcal disease (Streptococcus pneumoniae), Hib (Haemophilus influenzae type b) Tuberculosis (Mycobacterium tuberculosis) and Typhoid fever (Salmonella Typhi). However, the report warns that current Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis (TB) do not adequately protect against TB and that the development of more effective vaccines against TB should be accelerated. The report continues to say that the other three vaccines are effective, and the number of people receiving them should be increased to help reduce the use of antibiotics and prevent further deaths from AMR.
    
The report noted that the bacteria included in the priority pathogens list pose a significant threat specifically because of their resistance to antibiotics, however these pathogens currently have a weak vaccine pipeline with regards to the number of candidates and feasibility, so other interventions should be urgently pursued to prevent resistant infections.
    
Dr. Hanan Balkhy, WHO assistant director-general for antimicrobial resistance said: “Affordable and equitable access to life-saving vaccines such as those against pneumococcus, are urgently needed to save lives, and mitigate the rise of AMR.”
    
Dr. Haileyesus Getahun, director of WHO’s AMR Global Coordination Department said: “Disruptive approaches are needed to enrich the pipeline and accelerate vaccine development. The lessons from COVID-19 vaccine development and mRNA vaccines offer unique opportunities to explore for developing vaccines against bacteria.”


Challenges
The report also investigated some of the challenges facing those developing vaccines including with regards to pathogens associated with hospital-acquired infections.
    
Some of the difficulties include the challenge of defining target populations among all admitted hospital patients, the cost and complexity of vaccine efficacy trials and the lack of regulatory or policy precedent for vaccines against infections.
    
Dr. Kate O’Brien, director of WHO’s Department for Immunization, Vaccines and Biologicals said: “Vaccine development is expensive, and scientifically challenging, often with high failure rates, and for successful candidates complex regulatory and manufacturing requirements require further time. We have to leverage the lessons of COVID vaccine development and speed up our search for vaccines to address AMR.”
    
With AMR becoming an ever increasing global threat, many lines of attack are needed. The increase in vaccinations to tackle AMR bacterial pathogens is just one of the approaches, with others including reducing the spread and reducing the use of antibiotics. If and when more vaccines are created, they will no doubt have an effect. However, as noted in the report, it is important that the vaccines reach those most in need and are affordable to health systems all over the world.