Ten million people — equivalent to approximately one-quarter of the Canadian population — are expected to die annually due to antimicrobial resistance (AMR) worldwide by 2050. Researchers in Dr. Manish Sadarangani’s lab at the Vaccine Evaluation Center at BC Children’s argue that targeted vaccines are needed to help reduce such loss of life.
University of British Columbia (UBC) master’s student Liam Mullins and UBC doctoral student Emily Mason are joint first authors of a concise commentary about this issue that was recently published in PLOS Pathogens.
They report there’s been a stall in the development of new antibiotics while incidence rates of AMR have rocketed over the last 30 years.
“We’re not going to solve antimicrobial resistance without vaccines,” says Dr. Sadarangani, director of the Vaccine Evaluation Center.
What is antimicrobial resistance?
According to the World Health Organization — for which Dr. Sadarangani is on the Technical Advisory Group on Vaccines and Antimicrobial Resistance — AMR occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines. This makes infections much harder to treat, increasing the risk of disease spread, severe illness and death.
“The discovery and development of vaccines nearly a century ago was a crucial turning point in medical history,” says Dr. Sadarangani, associate professor in the Department of Pediatrics at UBC. Today, we have become accustomed to young children being easily treated for, or never even encountering, some of the scariest diseases that used to haunt humanity. It’s a world we don’t want to return to.”
Why use vaccines to combat AMR?
Vaccines prevent infection. The more you reduce bacterial infections, the less they’ll spread, the lower the related antibiotic use, and, thus, the spread of resistance is decreased.
Vaccines have successfully lessened cases of diphtheria, meningitis, whooping cough, ear infections, sepsis and pneumonia in children, immunocompromised and older people over the last century.
Moreover, antibiotics are not being developed at the speed necessary to keep up with the evolution of bacterial AMR. Strategies to preserve antibiotics for when they’re truly needed are critical.
Other strategies used against AMR include infection control and antibiotic stewardship policies.
Who would vaccines against AMR benefit most?
Interventions would benefit those at the highest risk of infection and death the most:
- people in low- and middle-income countries,
- individuals who are immunocompromised or have other health conditions such as diabetes, and
- children, who are often excluded from studies investigating new antimicrobials.
Pediatric antimicrobial development includes several hurdles. The need for different dosages or formulations can lead to technological and regulatory challenges, yet children are some of the highest antibiotic users in any age group, outside of older adults.
Vaccines can — and should — be developed specifically for their target demographic.
What are the challenges to developing vaccines for AMR bacteria?
Bacteria can challenge vaccine development through their high genetic diversity, a range of potential antigens and the ability to cause different outcomes depending on the health of the individual. It’s difficult to develop a vaccine that can provide protection across numerous strains of bacteria. Multicomponent vaccines are developed to broaden coverage and prevent vaccine resistance due to mutations, but this remains challenging.
When vaccines are developed with the goal of combatting AMR, both the host and the pathogen need to be considered.
What are you working on?
Dr. Sadarangani, Mason and Mullins work on vaccine design and development for Klebsiella pneumoniae bacteria, which can cause pneumonia, meningitis, and bloodstream, wound or surgical site infections, and is often resistant to many antimicrobials. They recently received numerous strains of Klebsiella that they will study to determine which are the most relevant globally for vaccine design. These researchers are examining protein expression using proteomics, the study of the interactions, function, composition and structures of proteins and their cellular activities, in microbial vaccine development. Mason investigates the immune response to serious bacterial infections and Mullins investigates the utility of bacterial outer membrane vesicles for vaccination.
