NAIROBI — With antimicrobial resistance (AMR) on the rise globally, the World Health Organization (WHO) Tuesday issued an urgent call to step up investment and research into vaccine candidates that can tackle the problem of drug-resistant bacteria in a new report that looks at key research gaps and opportunities. 

Antimicrobial resistance, which refers to bacteria, viruses and parasites that are resistant to drug treatment, results from factors such as the overuse and misuse of antibiotics and other antimicrobials in human and animal health.

But along with new drugs, the development of new vaccines can also help counter the problem, experts say.

“Vaccines are highly vital tools in fighting AMR,” Isabel Frost, lead author of the analysis, told a virtual press briefing on Monday. “This analysis was needed to understand where opportunities for development were, and where there might be some vaccines available in the near future to fight some pathogens.”

Infections from drug resistant pathogens are the third leading cause of death after cardiovascular diseases. Some 1.27 million deaths were attributable to AMR in 2019, while nearly 5 million deaths were somehow associated with drug-resistant infections, according to a major study published in January  2022 in The Lancet. That is more people than the number of deaths from either HIV or malaria.

The death rate was highest in western Sub-Saharan Africa, where there were 27.3 deaths per 100,000 people. It was lowest in Australia, where there were 6.5 deaths per 100,000 people, according to the Lancet study of January 2022, published by the Global Burden of Disease Collaborative Network, led by the Seattle-based Institute of Health Metrics and Evaluation (IHME).

The World Bank estimates that by 2050, infections associated with AMR will cause 28 million more people to fall into poverty, as a result of catastrophic illness, as well as adding US$1 trillion in healthcare costs.

AMR pathogens are a silent pandemic that threaten global public health 

The report is the first to provide a detailed analysis of vaccines in development that have the potential to address drug resistance from priority pathogens. It also draws attention to a need to accelerate trials in AMR vaccines, and makes a case for increased investment that can lead to more global health equity.

For instance, vaccines with varying degrees of efficacy already exist for dealing with four priority pathogens: Streptococcus pneumoniae, Haemophilus influenza type B, Salmonella Typhi, and microbacterium tuberculosis. (In the case of the latter, there are advanced trials underway of new  TB candidate ‘subunit’ vaccines which could also be given in combination with the old BCG vaccine). But their uptake and access vary globally, in yet another example of the enormous inequities found in global public health.

On the other side of the spectrum, there are no vaccine candidates in clinical development against six bacterial infections on WHO’s list of priority list of drug resistant pathogens, including ones that commonly cause severe and chronic gastro-intestinal illness or blood, urinary track and lung infections: C. Jejuni, H. pylori, E. faecium, Enterobacter spp, A. baumanii and P. aerungi.

Having identified AMR as a silent pandemic, and in response to this major public health threat, WHO developed a global action plan in 2015 to combat AMR. 

The plan, adopted by the World Health Assembly (WHA) in May 2015, identifies five key strategic areas: 1) increasing awareness, surveillance and monitoring; 2) combating infection through control measures; 3) reducing inappropriate use of antimicrobials; 4) making an economic case for more investment in diagnostics, antimicrobials and new treatments; and 5) the need for vaccines to combat AMR.

WHO priority pathogen list for research and development of new vaccine candidates 

In 2017, WHO developed the first list of bacteria  for which new antibiotics are urgently needed. The intent was to curb AMR and develop an analysis to inform R&D, investment decisions and policy actions globally.

Those considered to be “priority pathogens” are ones that pose the greatest global health threat because of their widespread resistance to common drugs, according to Frost, who also works as a WHO consultant for the Department of Immunization, Vaccines and Biologicals.

“We have identified 61 vaccine candidates in active clinical development against these pathogens,” she told Health Policy Watch, but noted some pathogens in this list are challenging targets for vaccine development.

Vaccine equity still hampered by poor distribution, access and uptake in most vulnerable regions

Streptococcus pneumoniae remains the leading cause of death from resistant bacteria; it caused 122,000 deaths in 2019. “These deaths are concentrated in countries that have the lowest levels of access not only to vaccines but to antibiotics and other health services,” Frost said.

“The good news is there are several vaccine candidates in late stage clinical development that have the potential to impact AMR. These include TB, e-coli and gonorrhea,” she added.

But vaccine development is expensive, and failure rates are high, Frost noted, so even getting some of the vaccines into advanced stages of development doesn’t mean all of them will reach the market. Clinical trials also typically need large populations and take years to complete before vaccines reach the licensing and manufacturing stages.

And she laments the fact that there are still no vaccine candidates in clinical development against six key bacterial pathogens on WHO’s list of priority list.: C. Jejuni, H. pylori, E. faecium, Enterobacter spp, A. baumanii and P. aerungi.

Dr. Dr. Mateusz Hasso Agopdowicz, a WHO technical officer, noted many challenges remain to increase coverage of existing vaccines, especially for vulnerable populations in low- and middle-income countries where they are needed most.

“To introduce new vaccines and increase coverage of existing vaccines,” he said, “we need sufficient funding for vaccination campaigns [and to] look for cheaper methods of developing vaccines, alternative ways of vaccine administration, and delivery as well as addressing vaccine hesitancy.”

Investment in research and development vital to keep priority pathogens in check

More resources are needed to continue R&D for vaccines in clinical development. And for pathogens with new vaccines in late-stage clinical trials, like microbacterium tuberculosis, funds are needed to accelerate these trials so tthey’re finished and the vaccines made available for use.

And last month WHO raised the red flag over the lack of new antibacterial treatments being developed to address the mounting threat of antimicrobial resistance (AMR).

Agopdowicz emphasised the need for further analysis to establish demand trends for vaccines so researchers can determine the number of doses needed when vaccines are ready to be used. “For the next 10 years, we need to use alternative approaches to contain resistant pathogens and use disruptive ways of vaccine manufacturing like mRNA,” he said.

Even with promising vaccine candidates in the pipeline, questions remain around IP rights and trade issues that could hinder global vaccine equity.

“No one benefits unless vaccines are created and then delivered to everyone who needs them,” said Boston University law professor Kevin Outterson, who is executive director at Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). “This is exactly why every CARB-X-supported product is backed by a contractual promise to avoid the issues with access to COVID vaccines.”

Image Credits: Richard Nyberg, USAID.