Research Groups
Mammalian Biology: Malaria
Research Interests and Description
Research Interests
Characterization of P. falciparum proteins as novel drug targets and vaccine candidates, development of malaria vaccines for clinical trials, design and synthesis of peptide based therapeutics, vaccine candidates and delivery platforms.
Description of Research
Malaria immunity and vaccine research
Research focuses on the development of combination malaria vaccines for both P. falciparum and P. vivax, based on the major merozoite surface proteins, responsible for protective immune responses in the host.
The main focus of research is: (a) characterization of vaccine target antigens, mostly from the erythrocytic stages of human malaria parasites, and (b) development of chimeric immunogens based on immunologically relevant regions of blood stage malaric antigens. A chimeric protein based on Pf MSP-3 and the C-terminal fragment of Pf MSP-1 has shown good promise in animal models. Protocols for preparing the fusion protein on a laboratory scale have been developed. The Malaria Group at ICGEB has established an expanded malaria vaccine development program which should enable us to take experimental malaria vaccines to clinical trials. A recombinant malaria vaccine candidate, named JAIVAC-1 against P. falciparum has entered a Phase I, first-in-man clinical trial, in August 2010. This expanded program is being supported by national and international funding agencies. A robust pipeline of novel antigens is also being created. The goal is to narrow the choice of candidate antigens to three or four to create a combination malaria vaccine.
Synthethic peptides as immunogens, peptidomemetics drugs and self assembling peptides as delivery agents
We have an ongoing programme on design and synthesis of conformationally restricted peptides containing non-protein amino acids, which can stabilize secondary structures like β-turns and helical structures in model peptides. More recently, we have used these design principles in:
a) design and synthesis of medium sized helical, basic peptides as novel antibiotics. Some of these peptides have shown activity in the low micro molar range and have the potential to move to the development stage, in collaboration with pharma industry;
b) design of peptide based inhibitors of amyloid formulation of polypeptide involved in diseases like Alzheimers (A β 42) and type2-diabetes (hIPP);
c) use of natural and modified amino acids as basic building blocks of small peptides that can self assemble in nanotubular, nanovesicular, and as hydrogel structures. Dipeptide based, self assembled structures are highly stable in different conditions and these biodegradable nanostructures have exciting potential as delivery vehicles for drug-like molecules, modified immunogens and as a matrix for three dimensional cell growth. In-vivo studies in mice are underway.
Designing synthetic immunogenes for neutralizing antibodies against HIV
In a separate programme, supported by the International Aids Vaccine Initiative (IAVI) and the Department of Biotechnology, we are developing conformationally restricted peptides based on the major B-cell epitopes from the gp41 protein of the HIV. Several peptides, ranging from 14 to 25 residues, have been synthesized and tested for their potential for providing viral neutralizing antibodies. A few of these peptides have shown reasonable neutralization activity against a range of viral isolates. Presentation of the conserved, relevant epitopes that bind to broadly neutralizing monoclonal antibodies, like 4E10 and 2F5, in their native conformation using structurally well defined protein scaffolds like cholera toxin is also part of this activity.
Biomarker discovery for infectious diseases such as TB and Malaria
The major focus is to use metabolomic approaches to investigate whether altered metabolic profiles can be identified as biomarkers for diagnostics and monitoring of disease using urine and breath as biological matrices. We have compared Volatile Organic Compounds (VOC’s) of tuberculosis patients and healthy individuals. Initial results are very encouraging and it seems that a signature of VOC(s) comprising more than one VOC’s can successfully discriminate disease from healthy individuals.
Recent Publications
Banday, K.M., Pasikanti, K.K., Chan, E.C.Y., Singla, R., Rao, K.V.S., Chauhan, V.S., Nanda, R.K. 2011. Use of Urine Volatile Organic Compounds to discriminate tuberculosis patients from healthy subjects. Anal Chem 83, 5526-5534 PubMed link
Chandele, A., Mukerjee, P., Das, G., Ahmed, R., Chauhan, V.S. 2011. Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii. Immunology 132, 273-286 PubMed link
Gupta, M., Chauhan, V.S. 2011. De novo design of α, β-didehydrophenylalanine containing dipeptides: from models to application. Biopolymers 95, 161-173 PubMed link
Parween, S., Gupta, P.K., Chauhan, V.S. 2011.Induction of humoral immune response against PfMSP-1(19) and PvMSP-1(19) using gold nanoparticles along with alum. Vaccine 29, 2451-60 PubMed link
Mazumdar, S., Mukherjee, P., Yazdani, S.S., Jain, S.K., Mohmmed, A., Chauhan, V.S. 2010. Plasmodium falciparum merozoite surface protein 1 (MSP-1)-MSP-3 chimeric protein: immunogenicity determined with human-compatible adjuvants and induction of protective immune response. Infect Immun 78, 872-883 PubMed link
Panda, J.J., Dua, R., Mishra, A., Mittra, B., Chauhan, V.S. 2010. 3D Cell Growth and Proliferation on a RGD Functionalized Nanofibrillar Hydrogel Based on a Conformationally Restricted Residue Containing Dipeptide. ACS Appl Mater Interfaces 2, 2839-2848 PubMed link
