The KaVA program was launched in 2021 and is led by Anurag Adhikari, PhD (Department of Infection and Immunology, KRIBS), who is an immunologist working to understand the functional aspect of humoral immunity in infectious diseases. Over the last 4 years, Dr Adhikari has developed in-vitro assays to quantify the antibody-mediated immune effector functions in Hepatitis C virus infection, which was later adapted to study the SARS-CoV-2 infection as well [1-4].
In the Nepalese context, the understanding of infection-associated immunity is severely limited, which has constrained our understanding of pathogen-specific immune-priming and associated disease pathogenesis. This program aims to fill in this knowledge gap by studying these pathogen-specific immune responses to delineate the host-associated protective versus pathogenic immunity. In addition to generating evidences, this program aims to train young investigators to capacity build the immunology research in Nepal. As a direct outcome of the KaVA-program, we recently upgraded our laboratory facility here at KRIBS. This laboratory capacity building has enabled us to characterize the blood mononuclear immune cells isolated from patients with Human Immunodeficiency Virus infection.
At the KaVA-program, we aim to screen and characterize the antibodies produced during infection, which can exert diverse immune effector functions such as antibody-mediated viral neutralization, antibody-mediated cellular cytotoxicity, antibody-mediated cellular phagocytosis (defined as the polyfunctionality of antibody). The discovery of such polyfunctional antibodies through this program is expected to create evidence that may spearhead the development of disease diagnosis modules including low-cost rapid immunochromatography kits, as well as will help develop new therapeutic antibodies for the cure of such diseases. This program also aims to understand the vaccine-induced humoral immunity against viral infections which will help us understand the associated vaccine efficacy, along with its long-term immune sustenance pathways. The current studies in the KaVA-program are detailed below.
Human Immunodeficiency Virus (HIV)
Study title: Screening and characterization of polyfunctional broadly neutralizing antibodies (bnAbs) isolated from HIV infected individuals
Investigator: Anurag Adhikari, PhD
Funded by: European Research Council
Collaborator: University of Cologne, Germany
This exploratory pilot study aims to develop a framework to identify and characterize bnAbs capable of executing poly-immune effector functions including antibody-dependent phagocytosis and antibody-dependent cellular cytotoxicity. This framework allows us to isolate HIV-specific single B cells from patient peripheral blood mononuclear cells (PBMC) to synthesize the monoclonal anti-HIV antibodies in vitro [5,6]. We anticipate that the functional and structural information on these poly-effector monoclonal antibodies will help with the development of effective vaccines against HIV.
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anti-HIV bnAb based HIV vaccine design framework
Nat Rev Immunol 19, 77–78 (2019).
- Adhikari A, Abayasingam A, Rodrigo C, Agapiou D, Pandzic E, Brasher NA, Fernando BS, Keoshkerian E, Li H, Kim HN, Lord M. Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection. Journal of Immunology. 2022. https://pubmed.ncbi.nlm.nih.gov/36165172/
- Balachandran H, Phetsouphanh C, Agapiou D, Adhikari A, Rodrigo C, Hammoud M, Shrestha LB, Keoshkerian E, Gupta M, Turville S, Christ D. Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses. Cell Reports. 2022 Jan 18. https://pubmed.ncbi.nlm.nih.gov/35090598/
- Adhikari A, Eltahla A, Lloyd AR, Rodrigo C, Agapiou D, Bull RA, Tedla N. Optimisation and validation of a new method for antibody dependent cellular phagocytosis in hepatitis C virus infection. Journal of Immunological Methods. 2021. https://pubmed.ncbi.nlm.nih.gov/34147479/
- Brasher NA, Adhikari A, Lloyd AR, Tedla N, Bull RA. Hepatitis C Virus Epitope Immunodominance and B Cell Repertoire Diversity. Viruses. 2021. https://pubmed.ncbi.nlm.nih.gov/34070572/
- Klein F, Kroidl A, Hoelscher M, Geldmacher C, Wolf T, Maganga L, Nanfack A, Adhikari A. Large-Scale Isolation of Broadly Neutralizing Antibodies from a Diverse Hiv-1 Cohort: Universität zu Köln, 2021. https://books.google.com.au/books?id=Ny3szwEACAAJ.
- Schommers P, Kim DS, Schlotz M, et al. Dynamics and durability of HIV-1 neutralization are determined by viral replication. Nature Medicine. 2023. https://pubmed.ncbi.nlm.nih.gov/37957379/