Congratulations to BIPH affiliates Prof. Maria Del Pilar Perez Romero (Department of Biological Sciences) and Prof. Prakash D. Nallathamby (Berthiaume Institute for Precision Health; Aerospace and Mechanical Engineering) on receiving an NIH/NIAID R21 award, “Monoclonal Antibody-Conjugated Nanoparticles for Precision CMV Antiviral Delivery” (R21AI203022).
Cytomegalovirus (CMV) is one of the most clinically significant yet overlooked viral threats worldwide. Most people who carry the virus never notice it, but for immunocompromised patients and newborns it can cause severe complications, chronic inflammation, and increased morbidity and mortality. That burden is growing in the United States as the population of immunocompromised individuals expands, including solid organ transplant recipients and infants born with congenital CMV infection.
Treatment today relies mainly on the FDA-approved antiviral ganciclovir (GCV) and its oral prodrug valganciclovir. These drugs work, but they distribute throughout the body rather than to infected cells, which blunts their efficacy, drives serious systemic side effects, and limits the doses patients can tolerate. Drug resistance is a further and increasing concern. With no licensed CMV vaccine and no curative therapy, new strategies are urgently needed.
This project takes a different approach: rather than replacing the drug, it changes where the drug goes. The team will build a targeted therapeutic platform, PLGA@GCV-mAb, that pairs GCV-loaded poly(lactic-co-glycolic acid) nanoparticles with monoclonal antibodies specific to the CMV envelope. The hypothesis is that this dual-functional system can deliver antiviral cargo selectively to infected cells, improving therapeutic efficacy while minimizing toxicity to healthy tissue.
The work is organized around two specific aims. The first will define the epitope specificity, antigen accessibility, and internalization dynamics of three previously isolated CMV-specific monoclonal antibodies, establishing which antibodies can best guide a nanoparticle into an infected cell. The second will engineer PLGA core-shell nanoparticles conjugated to those antibodies and functionally characterize them for selective antiviral delivery.
The award brings together complementary expertise at Notre Dame. Prof. Perez Romero, the project’s lead investigator, is a virologist whose laboratory studies CMV biology and host–virus interactions and isolated the antibodies at the heart of the platform. Prof. Nallathamby, Associate Director of Research at BIPH and head of the PD[N]ano Lab, develops targeted nanoparticle platforms for drug delivery and antimicrobial applications, including PLGA-based formulations.
The R21 mechanism supports early-stage, high-potential research, and this project (beginning September 2026) is designed to establish the feasibility of the platform and generate the data needed for larger follow-on studies. Because the antibody and the drug cargo are both interchangeable, the design is modular: if successful, the same approach could be adapted to other viral infections, allowing existing antivirals to be used more safely and effectively for the patients who need them most.
Research reported in this publication is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R21AI203022. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. PD. Nallathamby thanks Jesus for this miraculous opportunity to do good.
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