Lab Research: Major Areas

Even though designing a preventative CD8+ T cell based HIV/SIV vaccine may be extremely challenging, there is reason to believe that acute CD8 T cells may play a role in chronic virus suppression and a functional cure. We found that Mauritian cynomolgus macaques exhibit CD8+ cell mediated post-treatment control (PTC) of SIV replication after stopping antiretroviral therapy. We are currently evaluating whether PTC requires that these are virus-specific CD8+ cells or alternative types of CD8+ cells. We create SIV strains with point mutations to knockout epitope immunogenicity to eliminate the virus-specific CD8+ T cells in thes animals.

We also found that animals with PTC appear to establish small SIV reservoirs. Understanding how a small reservoir is established in Mauritian cynomolgus macaques, when compared to rhesus macaques, is also of interest to us. We hope that these unique attributes can be harnessed by other therapies to improve the host responses to virus infections.

During the COVID-19 pandemic, we helped our local community by supporting SARS-CoV-2 surveillance efforts. This included helping to develop a mobile saliva testing program in the summer of 2020, teaching local K-12 nurses how to run antigen tests in late 2020/early 2021, and developing an air surveillance program We have expanded and extended this air surveillance program with a focus on K-12 schools and skilled nursing facilities. We have close relationships with our local public health to share our data with the community. We will continue air surveillance to expand its access and improve its use in settings to keep our communities as healthy as possible.

The most common cause of morbidity and mortality in HIV+ individuals is Tuberculosis (TB). We have been working with Dr. Charles Scanga at the University of Pittsburgh to study host immune responses to M. tuberculosis in Mauritian cynomolgus macaques. Through this collaboration, we found that SIV infection specifically disrupts the ability to mount an effective immune response to M. tuberculosis, leading to more active TB disease.   We have explored the function of unconventional CD8+ T cells in both adult and juvenile animals infected with SIV and co-infected with M. tuberculosis. We have also learned that intravenous BCG administration to SIV-infected animals offers protection from TB. We are now evaluating whether an alternative BCG vaccine can confer protection from TB in SIV-infected juvenile macaques.

The development of the tools to molecularly barcode pathogens and then characterize them by deep sequencing has greatly facilitated our ability to study virus and bacterial dynamics upon infection. We have used barcoded SIV and M. tuberculosis. We can use barcoded SIV to track the number of individual virus lineages circulating in a host and that are present after stopping antiretroviral therapy. For M. tuberculosis, we can use the barcodes to track bacterial dissemination within a host. While these can be tricky experiments to execute, we are always interested in working with partners to implement these molecular tools in novel situations.

Within our lab, we have a Pathogen fee-for-service sequencing unit that is a component of Research Services at the Wisconsin National Primate Research Center. This unit is devoted to sequencing pathogens for clients both at UW and outside of UW. We have sequenced strains of SIV, HIV, ZIKV, SARS-CoV-2, and other viruses for numerous clients. We will sequence virus inocula for clients at no-charge because we believe that understanding the sequence of the virus used to infect animals is critical for ensuring rigor and reproducibility across studies. This service unit helps our lab’s sequencing skills continue to grow, lets us collaborate with other researchers, and provide a service to help other investigators.