Research Projects

The poultry industry is a rapidly expanding agri-sector in India. While agricultural crop production, which employs 49% of the nation's workforce, is increasing at a modest rate of 1.0-1.5% annually, the poultry industry is experiencing a growth rate of 8-10% per year. Consequently, India has become the third-largest producer of eggs and the fourth-largest producer of broiler meat globally, underscoring the sector's significant contribution to national nutrition and the economy. Despite significant achievements in the poultry industry, a major challenge impeding growth is the emergence of pathogens affecting poultry, leading to high mortality, production losses, and trade restrictions. Notable infectious diseases include infectious bursal disease (IBD), infectious bronchitis (IBV), and Newcastle disease (ND). Although antibiotic treatment is standard practice, recent report indicates that nearly two-thirds of poultry farms excessively use antibiotics to promote growth. This is concerning because studies have linked antibiotic overuse in poultry to antibiotic resistance in humans. The resolution of this issue largely depends on the development of novel vaccines targeting multiple poultry pathogens. Vaccination is central to poultry health management; however, current vaccines based on live attenuated, inactivated, or subunit antigens have limitations. Most traditionally used vaccines are injectables, requiring birds to undergo multiple immunizations within a short lifespan, which is challenging. Therefore, an oral vaccine platform that can solve antigen delivery and adjuvanting and is safe, scalable, economical, and easily administrable is needed. To overcome these limitations, our team developed unique recombinant outer membrane vesicles (rOMVs) for antigen delivery and a self-adjuvanting natural pathogen-mimetic vaccine platform. These rOMVs are nanoscale (~ 100 nm) particles shed from the outer membrane of hypervesiculating strains of E coli, retaining immune-modulating and adjuvant components of bacteria, including TLRs. Thus, rOMVs mimic non-infectious physical forms of bacteria. We have shown that rOMVs can display desired vaccine antigens singly or in combination, providing defined antigen delivery and adjuvant activity, making them a promising vaccine development platform. Additionally, we have been able to formulate rOMVs based tetravalent vaccine formulation against Dengue which shows high neutralizing capability against all the serotypes. Furthermore, OMVs are derived from the probiotic strain E. coli Nisslle 1917( EcN), which has been widely used to treat IBDs and diarrheal diseases, suggesting that rOMV derived from EcN might serve as a potential oral vaccine delivery system. Our preliminary findings revealed that oral gavage of rOMV-based vaccine triggers robust mucosal immunity with a high titer of secretory IgA antibodies, highlighting the potential of rOMVs as an oral vaccine formulation platform. In this context, we propose a highly innovative approach to i) clone, express, and purify rOMVs expressing immuno-dominant hemagglutinin-neuraminidase (HN), Spike Glycoprotein S-1, and viral capsid protein VP2 antigens/antigenic fragments from ND, IBV, and IBD viruses, respectively, and use them as oral vaccine formulations; ii) determine their immunogenicity with respect to the magnitude, quality, and persistence of antigen-specific B and T-cell responses following oral immunization in mice; iii) examine the efficacy of the above vaccine formulation in providing protection against IBD, IBV, and NDV viruses following immunization using and in-vitro infection and in vivo in challenge experiments in the appropriate models. The study is highly significant because it proposes a novel strategy that will overcome the current challenges in the design and development of a single oral vaccine formulation that is safe, affordable, and robust, providing long-lasting protective immunity against multiple poultry pathogens.