Translational Virology

Capacity enhancement of National Immunogenicity and Biologics Evaluation Center for assessing the immunogenicity of SARS-CoV-2 vaccines

Status- Ongoing

• PI:Dr. A.C. Mishra
• Funding agency: DBT-BIRAC
• Duration: Feb 2021-Jan 2023
• Sanctioned Budget: 1341 lakhs
• Brief Description/ Overview: Unprecedented collaborative efforts have been made all over the word to reduce duration of development of effective vaccines for COVID-19. This has resulted into development of many candidate vaccines in the country and in other places around the world. To maintain the speed and tempo of the vaccine development it is essential to develop and modernize the immunogenicity testing facilities for providing quality services matching to international standards to upcoming massive clinical trials. The present project aimed at establishing such a facility with sound quality system and advance tests for assessment of COVID-19 vaccines.

Establishment of National Centre for Immunogenicity Testing to evaluate vaccines in clinical trials

Status- Ongoing

• PI:Dr. A.C. Mishra
• Funding agency: BIRAC
• Sanctioned Budget: 1600 lakhs
• Brief Description/ Overview: Earlier, India was depended upon facilities abroad which are expensive and took a long time to give results causing delay in getting regulatory approvals for vaccines. Department of Communicable Diseases participated in a translational flagship Mission Program “Innovate in India (i3)” of Department of Biotechnology (DBT), Government of India to develop facility for providing vaccine immunogenicity and antiviral studies.
• Expected Outcome: Development of a world class facility for evaluation of the immunogenicity of vaccines & antiviral properties of drugs/preparations.

Evaluation of circulatory biomarkers for disease severity in hepatitis E

Status- Ongoing

• PI:Dr. Shubham Shrivastava
• Co-I: Dr. Vidya Arankalle (IRSHA), Dr. J Shastri, Dr. C Pawar (Kasturba Hospital, Mumbai), Dr. A L Kakrani (D Y Patil Medical College & Hospital, Pune), Dr. D G Bhosle (Bharati Vidyapeeth Medical College & Hospital, Pune)
• Funding agency: ICMR
• Sanctioned Budget: Rs. 91.95 lakhs
• Brief Description: Hepatitis E virus (HEV) infection accounts for ~50% of acute viral hepatitis cases in India. Pregnant women are at high risk of severe disease and mortality. In absence of specific treatment, identification of easily accessible disease severity predictors are of utmost importance for effective monitoring and treatment. So far, such biomarkers are not available. Our earlier studies showed that circulatory miR-122 and miR-134, could be biomarkers for severity. Further, based on whole transcriptome analysis, differential expression of defensins and molecules of S100 series was shown to be associated with clinical presentations of HEV infection. We propose to evaluate miR-122, miR-134, S100 proteins and alpha-defensins as potential serum biomarkers for severity of HEV infection.
• Expected Outcome: We aimed to provide systematic evaluation of four circulatory molecules as potential biomarkers for disease severity in hepatitis E.

Platelet derived exosomes and their role in endothelial dysfunction in dengue infection

Status- Ongoing

• PI:Dr. Shubham Shrivastava
• Co-I: Dr. Deepak G Bhosle (Bharati Vidyapeeth Medical College & Hospital)
• Funding agency: DBT-BioCARe
• Sanctioned Budget: Rs. 46,39,102
• Duration: 3 years, 2019-2022
• Brief Description: Dengue is the most common mosquito borne viral disease caused by one of the four dengue virus (DENV) serotypes. Severe dengue is associated with increased vascular permeability, hypovolemia due to plasma leakage and death. In dengue, platelets are one of the major cell populations affected by infection. Platelets are known to adhere to endothelium in case of any damage, however, how they dysregulate the function of endothelium in dengue infection is unknown. During viral infection, various cell types release extracellular vesicles, mainly exosomes in circulation. Exosomes play a crucial role in cell to cell communication by carrying functional mRNA and microRNA. With this background, our hypothesis is: DENV infection leads to activation of platelets which in turn releases exosomes in the circulation. These exosomes carrying microRNAs impair the function of vascular endothelium leading to severe dengue. The present study will explore the role of platelets in endothelial dysfunction in dengue infection.
• Expected Outcome: The present study will identify unique list of platelet derived, exosome associated microRNAs that may serve as potential biomarker of disease severity in dengue infection. The proposed study will explore the novel mechanism(s) underlying platelet mediated endothelial dysfunction in dengue infection.

Development of potent adjuvanted respiratory syncytial virus vaccine for mucosal delivery

Status- Ongoing

• I/CoPI:Dr. Harshad Patil
• Funding agency: DBT-Wellcome India Alliance
• Sanctioned Budget: 168 lakhs
• Brief Description/ Overview: Despite the large health impact of Respiratory Syncytial Virus (RSV) infections, a safe and effective vaccine is not available so far. The ideal RSV vaccine needs to overcome two hurdles: 1) it must induce the right type of immune response in infants, the major target group envisaged; and 2) should be suitable for administration via non-parenteral routes. Present proposal addresses these issues by developing a vaccine candidate that uses a novel combination of RSV virus-like particles and a single adjuvant that stimulates two pattern recognition receptors (PRR) and further assesses feasibility of sublingual or pulmonary delivery of the formulation.
• Expected Outcome: Development of VLP based candidate RSV vaccine

Evaluation of different adjuvants for development of potent chikungunya vaccine

Status- Completed

• PI/CoPI:Dr. Harshad Patil
• Funding agency: DST-SERB
• Sanctioned Budget: 32 lakhs
• Brief Description/ Overview: Though definite need is felt, long disappearance of CHIKV has been a concern for vaccine manufacture. Thus, research on development of safe, potent and economical CHIKV vaccine is lagging behind. Therefore, in this study we are evaluating inactivated chikungunya with various adjuvants by intradermal or intramuscular route for induction of cellular or humoral immune response
• Outcome: Dual PRR ligands induced superior antibody response, both qualitatively and quantitatively, than MPLA. Antigen dose reduction could be achieved after the use of chimeric adjuvant. In addition, i.d immunization using microneedles leads to better induction of neutralizing antibodies

Establishment of a novel Electronic Surveillance System for dengue in Pune: an initiative for Smart Cities Mission

Status- Completed

• PI:Dr. A C Mishra
• Co-I:Dr. Vidya Arankalle, Dr. Sanjay Lalwani, Dr. Arundhati G Diwan, Dr. Varsha Vaidya (Bharati Vidyapeeth Medical College), Anand P Kulkarni (Persistent Systems)
• Funding agency:ICMR
• Sanctioned Budget:400.1 lakhs
• Brief Description/ Overview:he present study is being undertaken for the establishment of a novel electronic system for dengue surveillance which will aid in better estimation of dengue prevalence and disease burden in Pune city.
• Objectives of the project: To develop web based electronic system to collect, store, retrieve and process data on dengue clinical spectrum, epidemiological parameters, vector density in selected areas of Pune city.
• selected areas of Pune city. To determine association of dengue cases with climatic conditions like rainfall, temperature, humidity and vector populations etc.
• Outcome:
• A cross-sectional, stratified serosurvey indicated high rate of transmission of dengue in Pune city with overall 81% of individuals were seropositive for dengue antibodies. The seroprevalence varied among 15 wards across the city from moderate high in Aundh (61.8%) to very high in Wanawadi (94.9%). There was an increasing trend of seropositivity with age, from 21.6% among < 36 months group to 77.3% in age group 16-18 years.
• In consecutive three-year (2017-2019) of disease surveillance indicated peak of dengue cases in the month of September-October. In all three seasons, all four dengue virus serotypes are co-circulating in Pune city and new clade of dengue serotype 4 was evolved.
• CDC-Epi-info software was customized to capture demographic , clinical and socio-economic status of dengue patients and able to demonstrate real time monitoring of positive and negative cases of dengue infection as spot or cluster on Pune map.

Immune response of Indian preterm infants to pentavalent vaccine

Status- Completed

• PI:Dr. Vidya Arankalle
• Funding agency: DHR-ICMR
• Sanctioned Budget- 40 lakhs
• Brief Description/ Overview: Primary aim of this project was to assess if the current national recommendations for pentavalent immunization of preterm infants are appropriate and ensure adequate immune response.
• Outcome-
• Comparative antibody response of Indian infants classified according to gestational age, to the component immunogens of the pentavalent vaccine is provided for the first time.
• It is satisfying to note that irrespective of gestational age, all the infants developed adequate antibody response against tetanus, diphtheria and, protective but lower antibody levels for HiB and hepatitis B.
• Suboptimal response to pertussis in all the infant groups emerged as a major concern.
• In addition to generating data on the relationship of circulating immune cells and cytokines with GA, the results revealed that both humoral and cellular immune responses of preterm infants were dependent on the type of the immunogen.
• Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

Prevalence of titers of Measles, Mumps, Rubella, Varicella antibodies in Indian infants and toddlers: A pilot study

Status- Completed

• PI:Dr Nandini Malshe (Bharati hopital)
• Co-PI: Dr Vidya Arankalle and Dr A.C. Mishra (IRSHA), Dr Sanjay Lalwani and Dr Sonali Palkar (Bharati hospital)
• Funding agency: GlaxoSmithKline (GSK) Pharmaceuticals
• Sanctioned Budget: Rs 86.66 lakhs
• Status: Completed
• Brief Description/ Overview: In view of the current unavailability of any recommendations on MMRV vaccine dose schedules, this study was conducted to assess the seroprevalence of IgM and IgG antibodies to measles, mumps, rubella and varicella at 6, 9, 12 and 15 months of age among the Indian infants.
• Outcome: This study demonstrated early disappearance of maternal antibodies against MMRV viruses leading to risk of these infections at an early age. The data thus emphasizes need for early immunization of Indian children. Further, observation of suboptimal response against measles vaccine warrants attention in view of the WHO initiative for measles eradication.

Norovirus surveillance among children with non-rotavirus associated gastroenteritis in Pune, India

Status- Completed

• PI:Dr Ruta Kulkarni
• Co-PI: Dr V. Kalrao (Bharati hospital), Dr S. Mankar (Mankar hospital), Dr M. Sangamnerkar (Chinmay hospital)
• Funding agency: Centers for Disease Control and Prevention (CDC), USA and intramural support from Bharati Vidyapeeth
• Sanctioned Budget: CDC, USA (Reagents for rotavirus and norovirus testing) and Bharati Vidyapeeth (Rs. 5 lakhs)
• Status: Completed
• Brief Description/ Overview: This project was undertaken as a part of a multicentric norovirus surveillance network in India, co-ordinated and partly sponsored by Centers for Disease Control and Prevention (CDC), USA. Noroviruses are the second most common cause of childhood gastroenteritis, after rotavirus which remains the leading cause. In view of rotavirus vaccine introduction in the national immunization program of India, it is important to study norovirus prevalence and epidemiology in the pre- and post-vaccine introduction period. For this purpose, a hospital-based surveillance was undertaken in Pune during 2018-2019. Children suffering from acute gastroenteritis were enrolled; faecal specimens of the enrolled children were analyzed for rotavirus and norovirus.
• Outcome: This project generated data on the prevalence, epidemiological characteristics and genetic diversity of norovirus infections among children in Pune. During 2018-2019, norovirus prevalence among children with non-rotavirus associated gastroenteritis in Pune was found to be 21.3%, and circulation of 5 different genotypes was observed.