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Indo-US VAP developing candidate vaccines for priority diseases

Y V Phani Raj, HyderabadThursday, July 27, 2006, 08:00 Hrs  [IST]

The Indo-US Vaccine Action Programme (VAP) has led to the development of candidate vaccines for rotaviral diarrhoea, malaria, HIV, tuberculosis, cholera, respiratory syncytial virus (RSV) Group A Streptococcus (GAS) etc. VAP has decided to develop revised roadmap based on priority diseases prevalent in both countries. Under the rotavirus project implemented at AIIMS- New Delhi, CDC-Atlanta and IISc-Bangalore and Stanford University, USA, phase-I clinical trials of the rotaviral diarrhoea vaccine strains (116E & I321) for the safety and immunogencity studies have been completed in India and USA using the vaccine in adults, older children and infants, suggesting that the vaccine is safe. Bharat Biotech has produced prototype vaccine 116E, under cGMP conditions which will now be pursued in larger clinical trials. In order to produce the vaccine indigenously, the company has developed vero-cell based vaccine. A double-blind randomized placebo controlled dose escalating phase Ib / IIa study has been planned to evaluate the safety and immunogenicity of live attenuated rotavirus vaccine 116E in healthy non- malnourished infants of 8-20 weeks of age. In the malaria project, the group at ICGEB, New Delhi, has carried out Pilot scale experiments to produce correctly folded recombinant PvRII (a P vivax duffy binding protein). PvRII produced at pilot scale has been used for immunogenicity studies in mice. Stability studies have also been performed. Lyophilization condition for recombinant PvRII has been developed. In a Hepatitis C study conducted at Deccan College of Medical Sciences & Allied Hospitals, Hyderabad and University of Tennessee Health Sciences Centre, Memphis, USA, 276 HCV infected samples for genotyping in North and South India (Hyderabad, New Delhi, and Lucknow) have been studied. Cloning and sequencing of the complete genome of HCV strain isolated from a single patient was carried out. The complete sequence was deposited in GenBank. Further comparative studies revealed that the Indian strains are closely related to Indonesian strains and there is high heterogeneity on gene sequences in envelope region. There has been progress in the area of Cancer immunotherapy. Studies were carried out at NCCS, Pune and UCLA School of Medicine, USA on cancer immunotherapy by antigen delivery and vaccination by genetically engineered dendritic cells (DCs). Using a model for prostate tumour, a leading cause of tumour-induced mortality in males, it has been demonstrated that CD40, a costimulatory molecule on DCs, dictates the homeostatic counter- regulation of inflammatory and anti-inflammatory immune responses. While CD40-induced inflammatory responses are associated with anti- tumour immunity, its counter-regulatory suppression by an exaggerated interleukin-10-mediated anti-inflammatory response, promotes tumour growth. The study has resulted in identification of a novel biological control system where the functional dichotomy of a costimulatory molecule self-limits its anti-tumour functions that can be manipulated for complete prevention of tumour development, establishment of host-protective prophylaxis and therapeutic auto-vaccination In studies conducted on Leishmania at the Institute of Pathology, New Delhi and CBER, FDA, USA on identification of virulence genes in Leishmania donovani, microarray hybridization was done. Analysis of these hybridizations yielded a number of clones showing differential expression between Leishmania life stages. Sequence analysis of some of the clones led to identification of several protein kinases. Studies conducted on Respiratory Syncytial Virus (RSV) at AIIMS, New Delhi and UAB School of Medicine, Alabama, USA have resulted in establishment of a prospective, community based investigation of viral incidence in children of India. A total of 1279 nasopharyngeal aspirates (NPAs) were tested and RSV was detected in 93 (7.3 per cent) NPAs. Phylogenetic analysis revealed that two genotypes of group A, GA2 and GA5 and BA, a newly identified group B genotype were prevalent during the study period. The present study reports the first nucleotide sequence analysis of G gene of RSV and will be useful for comparisons of candidate vaccine strains. This is also the first molecular characterization of paired RSV strains that have caused repeat infections in children from rural community in India. Year-long active surveillance studies have been planned at AIIMS and UAB School of Medicine to better define the epidemiology of human Metapneumovirus (hMPV).

 
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