Research - Ongoing Projects
My research is focused on the intersection of host pre-immunity and influenza infection/vaccination. The goal of my work is to understand how previous infections influence the outcome current vaccination and new viral challenges. This knowledge is then used to build the next generation of vaccines.
I use animal models, in vitro systems, and patient samples to obtain a picture of disease and its mechanisms.
Project 1. Influenza Immune Imprinting and Preimmunity
The concept of infant adaptive immunity remains poorly understood and loosely defined, especially in the context of influenza infection. The paucity of information regarding immune responses during viral infections in the extreme young stems from the previous absence of a translatable research model. Using human epidemiological and serological studies, it has been proposed that a person’s first influenza infection during youth imprints the immune system thereby affecting immune responses to subsequent influenza infections later in life. This phenomenon is called “influenza imprinting” or “immune imprinting.”
I am currently investigating how imprinting of various influenza and other respiratory viruses such as RSV skew the individual immune responses during each subsequent respiratory infection. Influenza disease and vaccination has not been previously investigated under the lens of the immune background. The findings from this project are significant to the design of future influenza vaccines and vaccination strategies, and for predicting susceptible populations during seasonal and pandemic influenza outbreaks.
Project 2. Influenza Vaccination Mechanisms - The Search for a Universal Vaccine
The use of vaccines to generate immunity to influenza viruses is at a critical turning point. The emergence of highly pathogenic avian viruses and the constant mutation of circulating strains have made traditional influenza vaccines and antivirals less effective, impractical, and costly. The HA protein is most immunodominant molecule of the influenza virus and the basis of seasonal influenza vaccines, is also the protein with the highest rate of change. The proposal of a universal influenza vaccine which could generate broadly reactive antibodies to several viral subtypes exists as a possible solution to the perpetual cycling of influenza vaccination.
This project aims to understand the interplay of the pre-immune host environment with the efficacy of vaccination specifically, influenza vaccines. I have established H1N1-, H3N2-, and H1N1->H3N2-pre-immune ferrets that are used for dissecting immunogenicity following vaccination with established and up-coming influenza vaccines. Findings so far have shown significant differences in the clinical protective responses of pre-immune vaccinated hosts compared to the naïve vaccinated hosts. The mechanisms of immune activation and vaccine efficacy are now being analyzed in terms of influenza HA antibody avidity, resident memory B cell populations, and T cell activation. The results from this project have significant impact on the design and strategies of future influenza vaccines.
Project 3. Emerging Viruses and the host-pathogen interaction
Emerging viruses are a constant but unpredictable threat to humans. As viruses emerge, there are many unknowns including host range, host susceptibility, pathogen reservoir, host tissue tropism, pathogenesis, transmission dynamics. Furthermore, the therapeutic treatments and prophylactic measures needed are often undefined.
I have established or been involved in several collaborations that focus on emerging pathogens in their countries of origin, for example MERS-Corona virus, Zika Virus and Chikungunya Virus. Having a facet of my research program devoted to emerging viruses allows the tools and disease models to be available for investigation of the emerging virus pathogenesis and the immediate development and testing of therapeutics. Influenza is a constantly emerging and re-emerging virus. Being ready for the next epidemic, pandemic, or zoonotic spillover of influenza or the previously uncharacterized novel virus is an important long-term goal of my research program.