Vaccinology

Dr. Sheela RamamoorthyDr. Sheela Ramamoorthy

Traditionally, vaccine-mediated immunity is generally studied in the context of the single antigen or pathogen, while in practice, the microbiome of the host, especially in the ecological niche and any co-administered antigen can influence the development of the immune response to the given antigen or pathogen. Currently, the influence of the bacterial microbiome on health and disease is better studied than that of the virome. Torque Teno Viruses are small DNA viruses, which chronically infect several mammalian species are ubiquitous. They are contaminants of the environment, water sources and biological products. They are epidemiologically associated with several human disease conditions, including respiratory disease, auto-immunity and cancer. However, it is not clear if they can act as primary human pathogens. In swine, experimental infection of gnotobiotic piglets results in microscopic tissue lesions and exacerbation of clinical signs due to coinfecting viruses. We are currently developing tools to study TTVs, understand alteration of immunity in co-infections e.g. with swine influenza viruses, with the eventual goal of understanding how their influence vaccine performance.

The number of newly emerging infectious diseases has increased rapidly over the last few decades, perhaps due to changing global traffic and trade practices. Over 80% of the newly emerging infections are caused by RNA viruses. The availability of rapid response vaccines and diagnostics are critical in limiting the extent of damage in the face of epidemics, especially for animal pathogens. The long lead development time for vaccines/diagnostics and policies surrounding licensure can result in delays which are detrimental to the timely control of the epidemic. The porcine epidemic diarrhea virus (PEDV) emerged in the U.S in 2013. It decimated a quarter of the U.S swine population within the first year. Using PEDV as a model, our efforts are focused on developing methods for novel first-response vaccines and diagnostics, with wide applicability to RNA viruses. As oral delivery would be a route of choice for epidemic vaccines, we are also exploring methods to improve oral vaccine delivery and thereby enhance the ease of epidemic vaccine deployment.

Porcine Reproductive and Respiratory Disease Syndrome Virus (PRRSV) and Porcine Circovirus strain 2 (PCV2) are two major viral agents that are co-detected about 80% of the time in porcine respiratory disease complex (PRDC) affected pigs. As a highly mutable Arterivirus, effective vaccine development against PRRSV is a long-standing challenge. Vaccines against PCV2 are highly effective in preventing clinical signs. Yet, new field strains of PCV2 continue to emerge periodically. Strong antibody responses are detectable within a week of infection with both viruses. However, they are suboptimal in protecting against disease or viral evolution. Our research efforts are focused on understanding the antigenic basis of the antibody response in PCV2 and PRRSV infections, with the goal of rationally engineering improved vaccine antigens to achieve greater efficacy.