David R. Martinez, PhD

The Martinez laboratory is actively conducting research in three broad areas: 1) understanding mucosal immunity of respiratory viral infections, 2) optimizing vaccination strategies against mosquito-borne viral diseases, and 3) refining our understanding of virus-mediated host neuroinflammation to ultimately intervene via vaccination to reduce neuroinflammation.

In area 1, understanding mucosal immunity of respiratory viral infections, my laboratory uses respiratory coronaviruses as model viruses. Respiratory viruses cause significant human disease each year. We use mouse models of coronavirus infection, SARS-CoV-2 and MERS-CoV, to understand which types of immune responses, such as mucosal IgA, generate durable protection against infection and disease. We then integrate this information to engineer mucosal vaccination strategies that can elicit the most desirable aspects of protective immunity. To this end, we are investigating how different vaccine platforms - mRNA-LNP vs. protein nanoparticle vaccines - and how the route of administration - systemic vs. mucosal - can elicit durable mucosal IgA responses in the upper and lower respiratory tract, and how these durable mucosal IgA responses protect against infection, disease, and transmission of highly pathogenic coronaviruses.

In area 2, optimizing vaccination strategies against mosquito-borne viral disease, my laboratory has designed several preclinical candidate vaccines against dengue virus as a model virus. Dengue virus is a mosquito-borne virus that causes >390 million infections in humans each year. We are currently studying the mechanisms by which mRNA-LNP vaccines can elicit long-lasting protective immunity against dengue virus. Immune responses to dengue virus can, in some cases, lead to more severe disease upon subsequent infections. We are currently engineering vaccines that aim to bypass this type of undesirable disease-enhancing activity by targeting non-canonical viral proteins that mediate host pathogenesis. Moreover, we are interested in understanding how vaccine platforms against dengue virus (e.g., mRNA-LNP vs. live-attenuated viral vaccines) differentially drive humoral immune responses in terms of antibody maturation, durability, and protection.

In area 3, we are investigating viral targets that can be exploited via vaccination using herpes simplex virus-1 (HSV-1) as a model virus. HSV-1 causes lifelong latent infections and is linked to the onset of neurodegenerative diseases, including Alzheimer's disease and dementia. We do not understand how lifelong viral infections, such as those caused by HSV-1, can raise the risk for the onset of neurodegenerative diseases. However, we do know that throughout the HSV-1 infection in people, stressors can cause HSV-1 to reactivate, leading to a range of symptoms ranging from blisters around the mouth to encephalitis. We are employing our expertise in vaccine immunology and mouse models of viral disease to understand how HSV-1 reactivation modulates neuroinflammation. In parallel, we are testing if experimental HSV-1 vaccination strategies can reduce various aspects of neuroinflammation caused by HSV-1 reactivation. We hope these experimental HSV-1 vaccines can someday be used not only to protect against HSV-1 transmission but perhaps also to lower the risk of onset of neurodegenerative disease.