Vaccines as key players in mitigating AMR (Part-I)

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The frequent and unregulated use of antibiotics was reflected in the 5 million deaths associated with antimicrobial resistance (AMR) in 2019 (1). Previously treatable bacterial infections contributed to many of these deaths, a case in point for the urgency of dealing with AMR.

Global scientific leaders brainstormed ways to include AMR management in health policy decisions. They promoted a multi-pronged approach which includes AMR surveillance, access to safe drinking water, reduced antibiotic use in livestock, and vaccine development. AMR is also a focus of the health priorities at the 2023 G20 summit (2).

In February 2023, a United Nations Environment Programme-backed global group recommended the usage of vaccines in animal husbandry and aquaculture to reduce antibiotic use (3). Vaccination for human use against infectious diseases is also supported by organizations such as CARB-X, ICARS, and BactiVac, among others.

While vaccines are essential tools in reducing antibiotic use, the deployability of vaccine programs is challenging. The efforts required to fast-track COVID vaccines, in terms of design and discovery, rapid authorization, and deployment, is preserved in our collective memory. Many advances in vaccine discovery, technology transfer, and licensure were made in the years of the COVID pandemic — all enabling a potent fight against a global threat. Scientists argue that if AMR can be prioritized as a global threat, the experience of the COVID urgency can be applied to vaccines against bacterial pathogens.

While popularly known to combat viral diseases, vaccines are equally potent in battling bacterial pathogens.

However, for the top six deadliest bacterial pathogens that took about 1 million lives in 2019 (E. coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter spp, Pseudomonas aeruginosa), a vaccine is available only against one — Streptococcus pneumoniae (1).

While there is a need for efficacious new antibiotics to manage bacterial infections, the use of vaccines will ensure the longevity of current as well as future antimicrobials.

With the published Lancet data estimating 22–24 deaths per 100,000 in sub-Saharan Africa and South Asia, the potential impact of vaccination in reducing antibiotic use in low and middle-income countries (LMICs) is immense. The burden of bacterial diseases due to specific pathogens is worrying. Vaccines for combating these bacterial pathogens offer hope in reducing poverty and lowering medical costs (4).

An encouraging development in the fight against AMR is the approval of two Indian pneumococcal conjugate vaccines , Pneumosil (Serum Institute of India) and PCV14 (Biological E). Pneumosil’s prequalification by WHO allows it to be procured by the United Nations and Gavi, potentially saving 400,00 global pediatric deaths annually (5).

Recently developed and rolled typhoid conjugate vaccine (against Salmonella typhi), too, has been a boon for natural disaster-struck countries. Multidrug-resistant typhoid incidence was significantly reduced upon vaccine introduction in Pakistan and Zimbabwe (6). With the 2022 Pakistan floods leading to a surge in typhoid cases, the importance of vaccines is highlighted in tackling the threat of AMR amidst climate-induced disasters.

The urgent focus for vaccine development, as determined by experts, lies in targeting Staphylococcus aureus, Klebsiella pneumoniae, E. coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp, and Helicobacter pylori. Targeting these pathogens can prevent not only frequently encountered cases of drug-resistant neonatal sepsis, hospital-acquired infections, and urinary tract infections, but also serious sequelae such as gastric adenocarcinoma (7).

Along with the need of fundamental research, innovations in the scale-up and delivery of vaccines will particularly benefit LMICs. But the ultimate success of these vaccines lies in their wide-spread acceptance by the general population. As vaccine hesitancy and antimicrobial resistance have been identified by WHO as the top threats of 2019. Appropriate awareness and policies will help spread the importance of vaccines against AMR. In the coming years, policy focus and design innovations will determine the momentum of vaccine programs in addressing the AMR issue.

Acknowledgements: This blog contains excerpts from the C-CAMP organized Webinar on ‘Vaccines for AMR’ in February 2023, as part of its CARB-X-GAN activity. The inputs from Dr. Padmini Srikantiah, Bill and Melinda Gates Foundation (BMGF) and Dr. Jyoti Joshi, International Centre for Antimicrobial Resistance Solutions (ICARS) during this webinar are duly acknowledged.

Funding call from CARB-X:

Calling innovators to apply for CARB-X funding to develop new oral therapeutics, vaccines for neonatal sepsis, and gonorrhea products.

The final deadline to apply for CARB-X funding is May 1, 2023.

Two free informational webinars will occur on April 20, 2023 (Register) and April 21, 2023 (Register).

For more information, visit CARB-X.org to review:

• Funding themes
• Dates and minimal requirements
• Application process
• Entering portfolio
• Apply page
• 40 min. video with info on the 2022–23 funding calls and how to apply
• Applicant questions page with FAQs that are updated regularly

Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however, this does not claim to be an exhaustive document on the subject. The mention of entities, networks, consortiums, or partnerships is merely to highlight the stakeholders working in the field and does not reflect attestations, validations or promotion of their work. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains.

Media on this topic relevant to the audience

1. Produced by Vaccines Today: How can vaccines help beat superbugs?
2. Slide from Dr. Srikantiah’s talk (to be used with permission) titled: “WHO action framework on vaccines to address AMR”[NJ15]

Sources:

1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis [published correction appears in Lancet. 2022 Oct 1;400(10358):1102]. Lancet. 2022;399(10325):629–655. doi:10.1016/S0140–6736(21)02724–0
2. G20 India Health Track: https://pib.gov.in/PressReleasePage.aspx?PRID=1891907
3. Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance: https://www.unep.org/resources/superbugs/environmental-action
4. Pecetta S, Nandi A, Weller C, et al. Vaccines for a sustainable planet. Sci Transl Med. 2023;15(685):eadf1093. doi:10.1126/scitranslmed.adf1093
5. PNEUMOSIL®, the new pneumococcal vaccine, achieves WHO prequalification, a key step toward improving access and affordability (https://markets.businessinsider.com/news/stocks/pneumosil-the-new-pneumococcal-vaccine-achieves-who-prequalification-a-key-step-toward-improving-access-and-affordability-1028849941)
6. “It’s difficult, but we’ll find a way”: a new vaccine against typhoid rolls out in a flood-devastated province of Pakistan: https://www.gavi.org/vaccineswork/its-difficult-well-find-way-new-vaccine-against-typhoid-rolls-out-flood-devastated
7. Frost I, Sati H, Garcia-Vello P, et al. The role of bacterial vaccines in the fight against antimicrobial resistance: an analysis of the preclinical and clinical development pipeline. Lancet Microbe. 2023;4(2):e113-e125. doi:10.1016/S2666–5247(22)00303–2