Projects

Protective antibodies against respiratory viruses

Infections caused by common respiratory viruses like respiratory syncytial virus, metapneumovirus, parainfluenza viruses, and coronaviruses are often considered trivial in healthy people but can be deadly in vulnerable patients. We are using highly sensitive techniques, including magnetic enrichment, fluorescent activated cell sorting, and functional screens to identify rare B cells that produce protective antibodies against viruses. We study the molecular interactions between these antibodies and viruses. We test the efficacy of our antibody candidates in preclinical models of infection. We also study viral evolution and the emergence of resistance in order to guide the development of next-generation antibodies.

Viral causes of LRTI in HCT recipients at the Fred Hutch

Protective antibodies against herpes viruses

Herpes viruses establish life-long infection by lying dormant in healthy people. Cytomegalovirus is a herpes virus that infects over 50% of the general population and can reactivate and cause devastating disease in immunocompromised patients, particularly patients undergoing hematopoietic stem cell or solid organ transplantation. Infection during pregnancy can also lead to neurodevelopmental disorders in children. Kaposi sarcoma associated herpes virus is another herpes virus that is particularly common in sub-Saharan Africa and causes several types of cancer. Similar to our respiratory virus project, we are studying rare B cells that produce protective antibodies against cytomegalovirus and Kaposi sarcoma associated herpes virus. We hope to leverage these antibodies to prevent and treat cytomegalovirus and Kaposi sarcoma associated herpes virus infections.

Research overview graphic — Research overview.
Created with BioRender.com

Antibody Engineering

The goal of this project is to break through the barriers that have traditionally limited monoclonal antibody use in transplant patients. We are engineering modifications into the Fc region of IgG1 to extend half-life and boost effector functions. These enhancements could reduce the number of doses, reduce the size of the dose, and boost efficacy. We are also optimizing the prevention and treatment of infections at mucosal barriers by optimizing antibody isotype, glycosylation, and route of delivery.

Illustration of enhanced antibodies — Enhanced antibodies.
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Pharmacokinetics of antibodies in hematopoietic stem cell transplant recipients

The goal of this project is to define the pharmacokinetics of monoclonal antibodies in hematopoietic stem cell transplant recipients. Evidence exists suggesting that the half-life of antibodies is significantly shortened in transplant recipients, and particularly in those who receive an allogeneic transplant. A better understanding of the kinetics of antibody decay in these vulnerable patients could help determine the timing of passive immunization to maximize protection. We are conducting a phase I clinic trial named COVIDMAB (NCT05135650) to address this knowledge gap.

Model of antibody decay and immune reconstitution in hematopoietic stem cell transplant (HCT) recipients.
Boonyaratanakornkit Lab

Immune reconstitution and correlates of protection in hematopoietic stem cell transplant recipients

Hematopoietic stem cell transplant recipients are most vulnerable to infection during the early post-transplant period; however, vaccination is also thought to be ineffective during this period because the immune system is not yet fully reconstituted. Effective vaccination relies on the presence of naïve antigen-specific B cells encoding a B cell receptor with the potential to bind the immunogen. The goal of this project is to define the kinetics of immune reconstitution for naïve B cells encoding a B cell receptor with the potential to bind common viruses. We are using highly-sensitive antigen-specific assays which could conceivably be leveraged in the future to personalize the timing of vaccination for individual transplant recipients as part of precision medicine. We are also following cohorts of immunocompromised patients to determine humoral immune correlates of protection to respiratory viral infections. These data would inform the target product profile for drug development to prevent and treat respiratory viral infections.