Research Projects

Major research directions

Cellular immunity to mRNA vaccines
The COVID-19 pandemic has seen a surge of scientific interest in mRNA vaccines, with a focus on the antibody response. In contrast, little is known about the T cell responses generated by these vaccines, e.g. where T cells traffic, tissue-resident memory responses, and what kinds of protection they can mediate. We will seek to understand the biology and protective effects of T cell responses generated by mRNA vaccines and the pathways of antigen presentation and innate immune activation that drive these responses in mice. For our early work in this area, see Laczko, Hogan, et al. Immunity (2020), PMID 32783919.​

Antibody/T cell collaboration
While many scientists cite the potential of T cells to protect from viral infections that escape neutralizing antibody responses (e.g. SARS-CoV-2), surprisingly little is known about the actual protective effects of T cells in a variety of acute viral infections. We hope to shed light in this area by studying a poorly understood phenomenon of antibody/T cell collaboration: intriguingly, neither CD8+ T cells nor non-neutralizing antibodies protect mice from influenza infection on their own, but they are super protective when combined, and we have no idea why! Unlocking this mystery may guide future vaccine design for influenza and other diseases. For early work on this topic, see Laidlaw et al., PLoS Pathogens (2013).​

Non-classical T cell immunity
CD8+ or killer T cells are conventionally known to recognize microbial peptides (epitopes) presented on classical MHC class I molecules (e.g. HLA-A, B, and C in humans). But in recent years, it has become apparent that CD8+ T cell responses are also mounted against epitopes presented on MHC-E, a family of non-classical MHC molecules that includes HLA-E in humans and Qa-1 in mice. Excitingly, these CD8+ T cells have shown a remarkable level of protection against simian immunodeficiency virus (SIV), a relative of HIV, in monkeys, although the mechanisms/functions distinguishing these from classical CD8+ T cells are not understood. We recently discovered an MHC-E-restricted CD8+ T cell response to influenza virus infection in mice, which offers a great model system in which to elucidate this biology. We next seek to describe the protective effect of this T cell response and the mechanisms behind its generation. Then, we aim to extend this line of study to other influenza epitopes and other viral infections, including SARS-CoV-2, murine cytomegalovirus, and potentially primate lentiviruses.

mRNA vaccine development for human and animal pathogens
We have extensive experience making mRNA vaccines in-house using the method developed by Weissman, Karikó, Pardi, and colleagues (i.e. nucleoside-modified mRNA delivered by lipid nanoparticles), and we published the first preclinical efficacy study of this platform in animal models of Zika virus infection in 2017. We're interested in further developing the mRNA vaccine technology to tackle some of the hardest disease targets with cellular immunity. We're also interested in developing more cost-effective mRNA vaccine designs for veterinary and agricultural applications. Potential targets of interest include viruses that affect fish, dogs, cats, pigs, cattle, and poultry.