Oral therapeutics and vaccines in battling AMR
Antimicrobial resistance (AMR) is emerging as one of the greatest public health concerns of our lifetime. The situation is particularly exacerbated in low-to-middle-income countries owing to the high burden of infectious diseases, inadequate healthcare infrastructure, and poor sanitation.
Six of the top ten causes of death in these countries are different infectious diseases. This scenario, combined with the growth in human migration in our well-connected world, makes a fertile ground for the emergence and spread of AMR. The need to tackle this global threat calls for collaborative, multi-disciplinary, and innovative AMR prevention and treatment strategies.
Preventive and Therapeutic Strategies
Infectious diseases can be tackled using two broad approaches, i.e., prevention and treatment. Generally, prevention strategies include using vaccines to train the immune system to mount a protective immune response upon encountering a pathogen. For example, the Bacillus Calmette–Guérin (BCG) vaccine is administered to children at around 28 days of age to protect against tuberculosis. Similarly, several other vaccines are administered to protect against different pathogens. In recent decades, many novel strategies for vaccine development have emerged. These include approaches that use multivalent vaccines, in which a single vaccine can protect against multiple pathogens.
On the other hand, treatment strategies comprise therapeutic compounds that can treat diseases caused by different pathogens either by alleviating the disease symptoms, stunting the pathogen’s growth, or killing the pathogen. Treatment strategies could involve using one or more drugs that perform the different above mentioned functions. Besides small molecule-based antibiotics, researchers are now exploring biologics like peptides and antibodies to treat AMR.
Route of Administration and Unmet Needs
For a vaccination or therapy to be effective, the route of administration plays a crucial role in addition to the efficacy of the vaccine or drug. Although intravenous injection of a therapeutic compound can ensure complete availability of the compound in patients’ bloodstream, patients may not comply with the method because it is invasive and painful.
On the other hand, oral administration of a vaccine or drug may ensure more patient compliance. However, only a fraction of the administered vaccine or drug reaches the bloodstream and becomes effective. Recent advances in drug delivery have enabled innovative approaches to ensure that much of the orally administered drug enters the bloodstream. These strategies include encapsulating the drug in a microcapsule that is degraded in the stomach, ensuring that the drug is released only in the intestine, and facilitating the absorption of most of it into the blood.
A classic example of an oral vaccine is the oral poliovirus vaccine (OPV), which helped eradicate polio in several countries, including India. The vaccine contains attenuated polioviruses that can replicate in the intestine but do not affect the central nervous system. It helps children develop an effective immune response against the poliovirus.
There is still a growing need for effective vaccines against several pathogens. For instance, the quest for a broad-spectrum vaccine targeted against sepsis-causing pathogens has been elusive. These include vaccines against pathogens, such as E. coli, K. pneumoniae, P. aeruginosa, E. faecium, A. baumannii, etc. Furthermore, there are no oral vaccines against pathogens that are stable enough to be transported and administered in different parts of the world. In the therapeutics landscape, there is a need to develop drug candidates to treat multi-drug resistant infections, e.g., multi-drug resistant tuberculosis.
Innovations in Oral Therapeutics and Vaccines
Many organizations worldwide are concentrating efforts on developing innovative strategies to develop oral therapeutics and vaccines.
Lumen Bioscience, a startup based in Washington, USA, supported by CARB-X, is developing a completely novel oral preventative for diarrhea caused by Campylobacter species and enterotoxigenic E. coli. The new product is a food-grade biologic cocktail containing monoclonal antibodies.
Bugworks, a startup based out of Delaware, USA, with R&D facilities at C-CAMP, Bangalore, is developing an antibacterial named GYROX. The drug inhibits two enzymes that bacteria need to replicate, gyrase and topoisomerase, and is amenable to oral and intravenous treatments for multidrug-resistant infections. Pre-clinical tests have been promising, with the compound effectively killing Gram-negative superbugs.
Foundation for Neglected Disease Research (FNDR), another C-CAMP incubatee, is developing drug candidates targeted to treat multi-drug resistant tuberculosis infections using different routes of administration.
PepThera, another startup based in C-CAMP, is developing peptide-based therapeutics to treat multi-drug-resistant bacterial infections.
Aristogene, also a venture at C-CAMP, has adopted an emerging strategy of pitting one microbe against the other to tackle AMR. Their cocktail of bacteriophages, called Colishield, selectively kills pathogenic E. coli.
Funding Support
In each of its new funding rounds, CARB-X supports three themes: oral therapeutics, vaccines for neonatal sepsis, and gonorrhea products. The scope for oral therapeutics encompasses agents targeting multi-drug resistant pathogens that cause a host of syndromes and infections, including respiratory tract infections and urinary tract infections, and that are prioritized by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC). The scope for oral therapeutics encompasses agents targeting multi-drug resistant pathogens that cause a host of syndromes and infections, including respiratory tract infections and urinary tract infections, and that are prioritized by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC). The scope for vaccines is focused on potential vaccines that can prevent neonatal sepsis by targeting bacteria such as K. pneumoniae, E. coli, A. baumannii, and S. aureus. The scope for gonorrhea products includes oral therapeutics, low-cost vaccines and rapid diagnostics. Entities can express interest in these themes by May 1, 2023, by 23:59 ET.
For more information, visit the Apply section at CARB-X.org, watch the 40-minute video with comprehensive information on the application process, and read the regularly updated FAQ page.
References
- https://polioeradication.org/polio-today/polio-prevention/the-vaccines/opv/
- https://www.dovepress.com/recent-advances-in-oral-nano-antibiotics-for-bacterial-infection-thera-peer-reviewed-fulltext-article-IJN
- https://www.uspharmacist.com/article/the-role-of-oral-antibiotics-in-bacterial-bloodstream-infections
- https://carb-x.org/carb-x-news/2022-funding-rounds/
- https://www.cdc.gov/drugresistance/biggest-threats.html
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. 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.
