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What is the role of vaccines in the battle against rising antimicrobial resistance?

Increasing antimicrobial resistance (AMR) has resulted in our inability to prevent or treat some infections caused by viruses, bacteria, fungi and parasites. AMR has become a major health threat around the globe. Some estimate that AMR may result in an additional 10 million deaths per year by 2050.1

Antimicrobial substances are frequently encountered in nature and it was their chance discovery by Fleming in 1928 that led to the modern era of life-saving treatment.

Microorganisms have evolved multiple mechanisms to escape the effect of these substances and it is therefore unsurprising that they have so quickly evaded newer treatments.

In contrast, vaccination primes an individual’s immune system, enabling defence against pathogens through multiple synergistic pathways. Resistance to these vaccine-primed defence mechanisms is very rare and vaccination is therefore a more durable intervention for preventing AMR emergence and combating infections with resistant organisms.

The development and use of effective, safe vaccines have therefore become vital for reducing and delaying the effects of AMR in human infection. Here we discuss the key roles which vaccines have in our increasing battle against the tide of antimicrobial resistance.

Direct prevention of AMR infection

Vaccines can protect against AMR by directly preventing infections caused by pathogens associated with resistance. Pneumococcal vaccines, for example, prevent Streptococcus pneumoniae infection, the most common cause of bacterial community-acquired pneumonia.

Pneumococcal infection is becoming increasingly resistant to penicillin-type antibiotics, which makes infection more difficult to treat. Use of the vaccine reduces the risk of infection and the incidence of AMR strains.

Vaccines reduce the total burden of infection rather than only those caused by AMR strains. This raises two important questions: firstly, is it possible to develop vaccines that generate protection against the mechanisms of resistance rather than the pathogen itself? Secondly, can we produce vaccines for pathogens in which antimicrobial resistance is commonplace, as this is likely to have the greatest impact in preventing the transmission of AMR.

While little progress has been made in specific AMR-vaccines, the WHO global priority list for antimicrobial resistant bacteria and a recent Vaccines for AMR report provides some direction for future research efforts.2,3

Indirectly reducing the drivers of AMR

Antibiotics are not effective against viruses such as influenza. Nevertheless, they are frequently prescribed for respiratory infections likely to be caused by viruses, which leads to alterations in the resident microbiome and drives resistance acquisition and selection in ‘bystander’ bacteria.

This is a widespread problem: almost half of the antibiotics prescribed for acute respiratory conditions in the United States, for example, are inappropriate.4 By reducing the number of respiratory infections through increased uptake of vaccines against common viruses such as influenza, we could have a significant impact in reducing this antibiotic use and removing this selection pressure.5-7

Furthermore, a minority of influenza cases are complicated by secondary bacterial pneumonia requiring antibiotics. Preventing the initial infection by vaccination would also reduce the risk of pneumonia, which would be especially important in the widespread AMR era.

Other population benefits from vaccination

There is accumulating evidence that some vaccines, particularly live vaccines such as measles vaccine, oral polio vaccine and Bacillus Calmette-Guerin (BCG), offer health benefits beyond providing protection against a specific pathogen.8

These off-target or non-specific effects (NSE) were first described after vaccine use for a measles outbreak in Guinea-Bissau. Although measles had largely disappeared after the epidemic, there was a striking fall in childhood mortality.9 Subsequently, similar observations of reduced all-cause mortality and fewer hospital admissions due to infection have been made in both low- and high-income settings.

While the mechanisms underlying vaccine NSE are not fully understood, these observations offer the prospect of tailoring the use of live vaccines to provide non-specific protection against AMR pathogens.

Until new treatment approaches can be developed, methods to prevent infection are vital to reducing transmission and spread of AMR. In addition to clean food, water and adequate sanitation, vaccination is a proven method for preventing infectious diseases. To maximise the benefit of vaccines in the battle against AMR, further development of vaccines for priority AMR pathogens, utilisation of existing vaccines for preventing inappropriate antimicrobial prescribing, and researching the additional non-specific benefits which vaccination may offer are vital parts of the strategy for tackling AMR.

1] O’Neill et al. Tackling Drug-Resistant Infections Globally. Review on Antimicrobial Resistance, May 2016. 2] World Health Organisation. Global Priority List of Antibiotic-resistant Bacteria to guide Research, Discovery, and Development of New Antibiotics, Feb 2017. 3] Wellcome Trust and the Boston Consulting Group. The Role of Vaccines in Combating Antimicrobial Resistance (AMR), 2019. 4] Fleming-Dutra et al. JAMA (2016). 3;315(17):1864-73. 5] Kwong et al. Clin Infect Dis (2009) 1;49(5):750-6. 6] Hardelid et al. J Antimicrob Chemother. 2018 1;73(3):779-786. 7] Maltezou et al, Clin Infect Dise (2013) 57(11):1520-6. 8] de Bree et al, Semin Immunol (2018) 39:35-43. 9] Aaby et al, J Infect (1984) 8(1):13-21.

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