Vaccines and anti-microbial resistance: a fascinating tango
There is a fascinating connection between vaccines and anti-microbial resistance (AMR); it relates to the dynamic interactions that they may exert on each other. Small changes in a vaccination strategy may generate a benefit or unwanted downward effects in AMR insurgence and spreading; on the other hand, strategies to tackle AMR cannot avoid encompassing vaccination campaigns. Furthermore, complexity is a common feature both for vaccination strategies and AMR.
This Special Focus is intended to update the topic of vaccines and AMR but containing complexity. The idea was to select a reduced number of papers that could summarize actual knowledge and perspectives on the role of existing and future vaccines in tackling AMR.
AMR is a silent pandemic that is estimated to cause around 1.3 million deaths annually globally, with close to 5 million deaths associated with AMRCitation1 and which is estimated to increase significantly up to 10 million annual deaths in 2050.Citation2 Such figures exceed deaths from cancer and diabetes combined, and they do not take into account the impact of being unable to safely perform high-risk medical procedures, such as complex surgery or chemotherapy.Citation3
The global community should continue to put efforts together to tackle AMR by finding ways to harmonize meaningful interventions in the One Health perspective.Citation4 To maintain the effectiveness of antibiotics over an extended period of time, we need to not only ensure appropriate use of antibiotics but as part of coordinated stewardship plan to maximize the impact of vaccination on AMR. Vaccines offer sustainable protection against AMR, as they are evolution-proof. Resistance among vaccines is less likely to evolve, and when it does, it is less harmful to human and animal health and well-being than drug resistance.Citation5 A consistent contribution to AMR containment policies will be reached by: a) increasing vaccine uptake; b) developing new vaccines that address prioritized AMR relevant pathogens; and c) filling the gaps in evidence generation of the benefits produced by vaccination.
Further research should investigate how best to establish the value of vaccines for AMR and to guide decision-making around allocating resources to the development and delivery of vaccines.Citation6,Citation7 In fact, some of the broader value elements relevant to vaccines are not (consistently) considered in Health Technology Assessment processes, including preventing AMR.Citation8 Improved value assessment criteria, including the health and economic benefits of AMR-relevant vaccines, are needed for existing and new vaccines. The inclusion of AMR and antibiotic prescribing as a reportable outcome in vaccine clinical trials should be encouraged, as this would strengthen the evidence base for the use of vaccines to control AMR. Vaccines against respiratory syncytial virus (RSV) may represent a first experience in this field. In 2020, WHO selected the priority disease areas for which vaccines were critically needed and available evidence supported a favorable technical feasibility assessment and potential impact on AMR.Citation9 RSV was defined as a very common respiratory tract infection that affects all ages even though most severe in early childhood. RSV was framed as an important driver of antibiotic use for undocumented respiratory illness globally and thus with a potential to reduce RSV-driven antibiotic use.Citation9 Recently, two vaccines for RSV in adults were approved in USACitation10 and one in Europe.Citation11 The evaluation at the Country level and consequent recommendations of RSV vaccines are expected to acknowledge, recognize and emphasize their role in tackling AMR as stated by WHO.
Commitments from national governments in National AMR Action Plans and from relevant scientific societies would lead the way for AMR relevant interventions at Country level. In the case of Italy, where antibiotic resistance represents a consistent problem,Citation12 the under-revision National Immunization PlanCitation13 and National AMR Containment PlanCitation14 were connected on this topic, and both acknowledge vaccines and vaccinations as tools to counteract AMR. Furthermore, 19 Italian scientific societies endorsed a position paper where vaccines and vaccination strategies, together with access to new antibiotics and the appropriate use of the existing ones, are the three pillars for a common strategy of tackling AMR.Citation15
New vaccines directed toward AMR relevant pathogens are difficult to be discovered and developed for a number of reasons. Nevertheless, new technologies for vaccine design and delivery are on the way. The first-ever vaccine specifically addressing Neisseria gonorrhoeae, a high priority among the WHO list of AMR relevant families of bacteria that pose the greatest threat to human health,Citation16 is starting phase I/II development.Citation17
All these topics are discussed across the papers of the Special Focus.
In summary, AMR is a threat not only to every aspect of modern medicine but also to global health security and economic growth. AMR is a complex problem driven by multiple, interrelated factors. It is an issue that can only be addressed through a holistic, collaborative and multi-sectorial approach. A compelling and growing evidence base shows that vaccines are an important complementary tool to reduce the threat of AMR. There is a need to fill the remaining gaps in the evidence base on the impact of vaccines on AMR, including the health economic case, and to establish their value as a complementary strategy in the fight against AMR. On the other hand, new vaccines for pathogens that pose a threat to human health, and especially for those resistant to antimicrobial medicines, are urgently needed.
Disclaimer
Federico Marchetti is a GSK Vaccines employee. His contribution to this edition is based on his expertise and does not reflect GSK’s position.
Disclosure statement
No potential conflict of interest was reported by the author(s).
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References
- Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399:629–55.
- O’Neill J. Tackling drug-resistant infections globally: final report and recommendations. Rev Antimicrob Resist. 2016. London: HM Government. doi:10.1016/j.jpha.2015.11.005.
- WHO. Global action plan on antimicrobial resistance. http://apps.who.int/iris/bitstream/handle/10665/193736/9789241509763_eng.pdf?sequence=.
- Vekemans J, Hasso-Agopsowicz M, Kang G, Hausdorff WP, Fiore A, Tayler E, Klemm EJ, Laxminarayan R, Srikantiah P, Friede M, et al. Leveraging vaccines to reduce antibiotic use and prevent antimicrobial resistance: a World Health Organization action framework. Clin Infect Dis. 2021;73(4):e1011–2. doi:10.1093/cid/ciab1062.
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- WHO. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25FebET_NM_WHO.pdf?ua=1.
- Vaccines Europe. The role of vaccination in reducing antimicrobial resistance (AMR). 2016 Nov. http://www.vaccineseurope.eu/wp-content/uploads/2016/11/VE-policy-paper-on-the-role-of-vaccines-in-reducing-AMR2016-FIN.pd.
- Bell E, Neri M, Steuten L. Towards a broader assessment of value in vaccines: the BRAVE way forward. Appl Health Econ Health Policy. 2022;20(1):105–11. doi:10.1007/s40258-021-00683-z.
- Leveraging vaccines to reduce antibiotic use and prevent antimicrobial resistance: an action framework: world health; 2020. Licence: CC BY-NC-SA 3.0 IGO.
- Kingwell K. RSV vaccines score landmark FDA approvals. Nat Rev Drug Discov News. 2023 May;31(7):523–5. doi:10.1038/d41573-023-00085-x.
- Arexvy. Recombinant respiratory syncytial virus pre-fusion F protein, adjuvanted with AS01E. EPAR. European Medicines Agency; 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/arexvy.
- WHO Regional Office for Europe/European Centre for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe 2022 – 2020 data. Copenhagen: WHO Regional Office for Europe; 2022. https://www.ecdc.europa.eu/sites/default/files/documents/Joint-WHO-ECDC-AMR-report-2022.pdf.
- Piano Nazionale di Prevenzione Vaccinale 2023-2025. https://www.quotidianosanita.it/allegati/allegato1679488094.pdf.
- Piano Nazionale di Contrasto all’Antibiotico-resistenza (PNCAR) 2022-2025. Ministero della Salute. https://www.salute.gov.it/imgs/C_17_pubblicazioni_3294_allegato.pdf.
- AMR Task Force Project. Recommendations for an effective strategy on antimicrobial resistance. Pharmadvances. 2022 Nov Special Issue;4(No. 4–Special):7–15. http://www.pharmadvances.com/recommendations-for-an-effective-strategy-on-antimicrobial-resistance/.
- WHO. List of bacteria for which new antibiotics are urgently needed. 2017. https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed.
- A phase 1/2, observer-blind, randomized, placebo-controlled multi-country study to assess safety and efficacy of GSK Neisseria Gonorrhoeae GMMA (NgG) investigational vaccine when administered to healthy adults 18 to 50 years of age. NCT05630859. Clinicaltrials.gov. https://classic.clinicaltrials.gov/ct2/show/NCT05630859.