Our Work
Developing Better Vaccines and Immune-Based Treatments for Viral Pandemics
Vaccines have improved health and life expectancy worldwide, but there are still viruses without effective vaccines such as HIV-1. SARS-CoV-2 vaccines prevent severe disease, but they do not always prevent infection. This underscores a critical need to develop better vaccines for current and future viral pandemics.
The goal of the Peñaloza lab is to develop more effective vaccines and treatments for viral infection. With this goal in mind, the lab has demonstrated that vaccines designed to selectively activate CD4 T cells can lead to lethal inflammation after viral infection, highlighting factors that dictate vaccine safety (Penaloza, Science, 2015) (Bhattacharyya, Immunology, 2017).
The Peñaloza lab has also shown that activation of TLR4 by products of the microbiome improves immunotherapy for chronic viral infection (Wang, PLOS Pathogens, 2018), and that transient IFN-I blockade improves vaccines against HIV-1 and other viruses (Palacio, JEM, 2019), demonstrating critical effects of innate immunity on virus-specific T cells and B cells.
Recently, the lab demonstrated that coronavirus vaccines do not need to be antigenically matched to confer protection. The lab showed that a SARS-CoV-1 vaccine developed 20 years ago can also protect against SARS-CoV-2 (Dangi, JCI, 2021). These data provide a proof-of-concept to improve vaccine preparedness for future coronavirus pandemics as one may consider stockpiling vaccines based on known coronavirus sequences and deploying them against genetically-related coronaviruses that could enter the population in the future.
Current SARS-CoV-2 vaccines and antibody therapies are based on the spike antigen, and although they can prevent severe disease, they do not always prevent infection. The Peñaloza lab demonstrated the improved efficacy of SARS-CoV-2 vaccines and antibody therapies targeting also the nucleocapsid antigen (Dangi, Cell Reports, 2021) (Dangi, JCI, 2022), and more recently our studies pinpointed novel strategies to improve SARS-CoV-2 and SIV vaccines by reducing the priming dose (Sanchez, Science Immunology, 2021) and by modulating pre-existing antibody responses (Dangi, Cell Reports, 2023).
As shown by all of this prior work, the overarching theme in the Peñaloza lab is to improve vaccines and immune-based antivirals, by understanding how innate immunity and different virus-specific responses aid in clearing viral infections.
The lab utilizes multiple viral infection models to elucidate basic mechanisms of immune regulation, with especial focus on developing HIV and coronavirus vaccines, starting from basic science.