Viruses are the tiniest of all microbes, but they can pack a powerful punch, infecting us with an array of diseases from chicken pox to COVID. Thankfully, vaccinations are able to largely mitigate these health concerns, and prevent diseases that can be dangerous or even deadly. We seek to strengthen our understanding of the immune response and apply new insights to vaccine development. The goal of our work is to prevent the morbidity and mortality associated with viral infections, especially in children or elderlies who suffer immunosuppression.  

Our research areas of interest can be classified into three major categories.

1. Mechanisms of immune defense against respiratory viruses at the mucosal surfaces, and the development of mucosal vaccine strategies. The mucosal immune system provides the first line of defense against pathogens that enter the body through the mucosal membrane. It comprises the largest immune organ in the body and can be viewed as a single layer of epithelium covered by mucus, in which the anti-microbial proteins are reinforced by innate and adaptive immune strategies. We are particularly interested in how respiratory viruses are captured, delivered, processed, and eventually sensed by the mucosal immune system. Moreover, how the effectors including sIgA, Trm, and Brm are orchestrated during their initiation, maintenance, and contraction phases. We aim to identify key players along the mucosa surface, which ideally and eventually serve as the targets for the next generation of vaccine design.

2. Factors to influence and strategies to improve vaccine performance. There is substantial variation between individuals in the immune response to vaccination. The possible mechanisms include intrinsic host factors, perinatal factors, and extrinsic factors. Further, environmental factors, behavioral factors, and nutritional factors also influence how individuals respond to vaccines. Moreover, vaccine factors and administration factors are also important. An understanding of all these factors and their impacts on the design of vaccine studies and decisions on vaccination schedules offers ways to improve vaccine immunogenicity and efficacy (Zimmermann and Curtis, 2019). Our most recent work involves the identification of a few administration methods and vaccine modalities that confer superior immune responses and protective efficacy, and dedicating to interrogating the underlying mechanisms. By using mRNA vaccine and adenoviral vectored vaccine as model systems, we aimed to identify key determinants that shape the optimal immune responses and further guide our routine immunization practices.

(Adapted from Review by Zimmermann and Curtis, 2019 C.M.R.)

3. Virus-host interactions. Another important piece of our research endeavors is keeping explore the mechanisms of antiviral factors. We previously characterized the interplay between a few essential pathogens, including HIV, ZIKV, SARS-CoV-2, and Mycobacteria tuberculosis, and host cellular factors, including IFITMs, TIM protein, and LY6E. We now extended our interests to respiratory viral pathogens, including influenza virus, Respiratory Synthia Virus, coronaviruses, and adenoviruses. In particular, we aim to characterize their tissue tropism, entry pathway, and early innate immune sensing, which is anticipated to foster advanced antiviral strategies. 

(Adapted from Schneider WM, et al. 2014. Annu. Rev. Immunol.)