2023 Department of Pediatrics Academic Annual Report

MOLECULAR DIAGNOSTIC VIROLOGY LABORATORY Under the leadership of Dr. Britt, the Molecular Diagnostic Virology Laboratory provides an essential service for the University of Alabama Hospital and Clinics and Children’s of Alabama. • Same-day diagnostic services of infections of the central nervous system (CNS) and respiratory system allows for targeted therapeutic approaches and the institution of relevant hospital infection control policies for hospitalized patients, resulting in improved patient care. This testing includes SARS-CoV-2, including variant sequencing. • Same-day turnaround for CNS viral infections is not available either commercially or at hospital laboratories other than the services provided by the Diagnostic Virology Laboratory. • Quantitative assays of herpesviruses are utilized for monitoring transplant recipients. • In addition, specialized testing is available upon request for investigation of hospital-acquired infections. • Assay development for specific agents, as required by clinical services at UAB and Children’s of Alabama. • Recently, he and COA colleagues identified an adeno-associated virus causing severe hepatitis in young children that received international attention. EMERGING INFECTIONS PROGRAM Stephanie Moore, Ph.D., and Dr. Whitley have built a team of experienced scientists in virology, viral immunology, pathogenesis and medicinal chemistry from eight partnering academic institutions, plus Southern Research, to develop small molecule therapeutics for the treatment of emerging viral infections under the umbrella of the Antiviral Drug Discovery and Development Center (AD3C). Members of several genera of RNA viruses that are major causes of human disease, bioterrorist threats or emerging infectious diseases are being studied. Projects focus on coronaviruses that cause SARS and MERS, alphaviruses that cause Venezuelan equine encephalitis virus and chikungunya, flaviviruses (dengue, West Nile virus, and Zika) and influenza A virus. The team utilizes the existing data and compounds to perform proof of principle studies in animal models, thereby delivering potential small molecule therapeutics to the government. Work performed by this team has been influential within the field as an effective model for drug discovery and development. The group has also evaluated a limited number of additional, novel compounds provided by collaborators at the Emory Institute for Drug Discovery (EIDD), Gilead Sciences and Pardes Biosciences. Expertise exists in the AD3C for IND preparation and filing as well as Phase I studies with adequate resources. The projects are supported by three Cores: Administrative, the Assay, and the Medicinal Chemistry and Lead Development. The organization and interaction between all projects and Cores are monitored by the Administrative Core. This collaboration has already contributed significant data to two INDs filed for SARS/MERS and two patents and proof of principle data for chikungunya, one for West Nile and additional patents being filed for coronavirus compounds. Importantly, Dr. Whitley recently received a grant to progress a lead molecule through pre-clinical toxicology toward a clinical trial for chikungunya. SARS-COV-2 PROGRAM At the beginning of the SARS-CoV-2 pandemic, leveraging their virology expertise, Drs. Boppana, Britt and Pinninti implemented a natural history study to determine virologic and immunologic characteristics of COVID-19 infections in children and established a biorepository of specimens (nasopharyngeal, nasal, saliva, rectal swabs and peripheral blood) from infected adults and children. Drs. Boppana, Britt and Pinninti successfully obtained funding from the National Cancer Institute to understand the relationship between adaptive immunity and SARS-CoV-2 replication in children undergoing cancer chemotherapy or other immunomodulatory treatments. They also received supplemental funding from NCI to examine immune responses and cardiac side effects following COVID-19 vaccination in this cohort (1U01CA260462-02S1). Drs. Boppana and Pinninti have been conducting Pfizer and Moderna COVID-19 vaccine trials in children between six months and 11 years of age and Pfizer anti-viral studies in children <12 years. More than 230 children have been enrolled in these trials since May 2021. With the emergence of new SARS-CoV-2 variants and subvariants, the vaccine trial protocols have been continually updated and adapted to include the newer bivalent vaccine. Additional vaccine trials by both Moderna and Pfizer are planned to enroll infants as young as 2 months to evaluate the safety and immunogenicity of the bivalent vaccines. SMARTT STUDY PROGRAM As one of almost 20 sites funded through the Pediatric HIV/AIDS Cohort Studies (PHACS) by NICHD and coordinated by Harvard College, the HIV-1 research program led by Cecelia Hutto, M.D., is participating in multiple protocols. For more than 15 years, the research team has enrolled and provided follow-up of participants in the Surveillance and Monitoring for ART Toxicities (SMARTT) protocol. The major focus of this study is evaluation of the effects of maternal exposure to ARVs, prescribed medications and substance abuse during pregnancy on health outcomes in their infants and children. The SMARTT study is the largest study of pregnant women living with HIV in the United States. Nationally, more than 4,000 participants have been enrolled since the beginning of the study. Locally, the team is following more than 200 children ranging in age from infancy to 18 years of age. Health outcomes that are monitored include growth, neurodevelopment, cardio metabolic, hearing and language, and neurologic function. The team also enrolls and follows participants in the Adolescent Master Protocol (AMP UP LITE), which includes those 18 years and older who were perinatally infected. The study is designed to define the long-term outcomes of HIV infection and antiretroviral therapy among young adults with perinatal infection as they age into adulthood. The research team recently began enrollment for a third protocol, Health Outcomes Around Pregnancy and Exposure to HIV/ARVs (HOPE). This study is designed to evaluate the health outcomes of women living with HIV over time. Data and biologic specimens from these protocols are available for investigators with research concepts to access for their studies. Data from the SMARTT study has been instrumental development of national and international guidelines for the care of women with HIV during pregnancy.

2023 Academic Annual Report

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