Development of a Self-Adjuvanting, Cross-Protective, Stable Intranasal Recombinant Vaccine for Shigellosis.

Baruah N, Ahamad N, Maiti S, Howlader DR, Bhaumik U, Patil VV, Chakrabarti MK, Koley H, Katti DS.

ACS Infect Dis. 2021 Dec 10;7(12):3182-3196.

Many infectious diseases continue to pose a major threat due to unavailability of vaccines. One such that pose a risk of breaking into epidemics is Shigellosis which causes fatal diarrheal disease and is notorious to acquire antibiotic resistance. Thus far no vaccines have been developed due to low immunogenicity as well as serotype specificity. Prof Dhirendra Katti’s group in collaboration with Prof. Hemant Koley at ICMR-National Institute of Cholera & Enteric Diseases, have developed a stable intranasal Vaccines against Shigella dysenteria. They took a rational approach to develop a vaccine wherein, conserved protein Sd1 from Shigella dysenteria and conserved immunogenic protein, IpaC were used. Using a detergent-based technology to stabilize the heterogenous complex of the two proteins, it was found to evoke a robust immune response when administered orally in BALB/c mice. The authors further displayed that the vaccine conferred protection not only against S. dysenteriae but also heterologous Shigella flexneri.

In conversation with the first author, Srinivasarao

Simultaneous amelioration of diabetic ocular complications in lens and retinal tissues using a non-invasive drug delivery system.

Srinivasarao DA, Sreenivasa Reddy S, Bhanuprakash Reddy G, Katti DS.

Int J Pharm. 2021 Oct 25; 608:121045.

How would you describe the major breakthrough of this study?
Srinivasarao:In this study, we succeeded in delivering two therapeutic agents [an antioxidant, pyrrolidine dithiocarbamate (PDTC) and an anti-VEGF agent, triamcinolone acetonide (TA)] simultaneously to anterior (lens) and posterior (retina) ocular tissues using polymeric core-shell nanoparticles (NPs). Further, controlled release of entrapped drugs (burst followed by sustained release of PDTC, whereas, a slow and sustained release of TA) was achieved using the fabricated delivery system. As a consequence, the developed drug delivery/therapeutic strategy minimized diabetes associated cataract and retinopathy in diabetic retinopathy rats.

What was the most challenging part of the study?
Srinivasarao:There are multiple experiments that were challenging, which include fabrication of NPs, generation of diabetic retinopathy rat model and characterization of pathological markers in ocular tissues. However, the most challenging part that I felt was the fabrication of nanoparticles and optimization of drug loading in nanoparticles so as to achieve sequential drug release.

How did the collaboration with NIN facilitate the study?
Srinivasarao:Our collaboration with NIN Hyderabad accelerated progress of the in vivo study. NIN offered state-of-the-art facilities for animal studies i.e., housing of animals, generation of diabetic retinopathy animal model, characterization of oxidative stress and neovascularization markers in lens and retinal tissues.

In conversation with the first author, Aman Nikhil

Evaluating potential of tissue-engineered cryogels and chondrocyte derived exosomes in articular cartilage repair.

Nikhil Aman and Kumar Ashok.

Biotechnol Bioeng. 2021 Nov 1.

What gap does your study addresses?
Aman Nikhil: Cartilage repair still faces limitations like phenotype instability and poor integration with surrounding tissue. In our study, we utilized chondrocyte exosomes as paracrine signaling molecules which will help to maintain the phenotype of formed cartilage. Further, these exosomes were utilized in combination with chondroitin sulfate releasing cryogel which was shown to act as exosome delivery system and due to its properties of high compressibility and elasticity, it will integrate well on swelling with the defect area.

What was the most challenging part of the study?
Aman Nikhil: In this study we strived to utilize chondrocyte exosomes as a cell free therapy and designing different cryogel scaffolds to better mimic the architecture and constituents of the cartilage and subchondral bone. So, we proposed the combinatorial approach of exosome laden cryogels for cartilage regeneration. Further, to overcome the problem of delamination of bi-layered cryogel, the two layers were joined in single cross-linking reaction with gelatin as a common polymer in both layers.

How do you evaluate the translation potential of this study?
Aman Nikhil: To evaluate the translation potential, animal experimentation is required where the potential of these exosome laden cryogels can be evaluated. For cartilage, higher animal models like goat, sheep or horse are preferred because of the similarity of their stifle joint to humans. Although preliminary studies can be performed in rabbit (Gupta et al., 2017) where the biocompatibility and regeneration potential can be tested.

Where do you see the application of this study, particularly in the Indian context?
Aman Nikhil: Indian population is prone to osteoarthritis (OA) which is musculoskeletal joint disorder affecting cartilage having prevalence of 22% to 39%. Approximately, 45% of women over the age of 65 have OA related symptoms (Cui et al., 2020). In addition, trauma injuries (accidents, sports injuries) also cause damage to knee cartilage and subchondral bone. So, tissue engineering strategy mentioned in this study has application for treatment of such osteochondral defects.

Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. 2020. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine 29:100587.
Gupta A, Bhat S, Chaudhari BP, Gupta KC, Tägil M, Zheng MH, Kumar A, Lidgren L. 2017. Cell factory‐derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits. J. Tissue Eng. Regen. Med. 11:1689–1700. https://doi.org/10.1002/term.2063.