Passive immunotherapy for measles infection

Measles (MeV) causes disease worldwide despite efforts towards eradication by vaccine, primarily because it is readily spread between people. Acute MeV infection causes immune amnesia, increasing susceptibility to other infectious diseases. In addition, rare but severe neurological complications can develop several years after measles due to persistent MeV infection of the central nervous system (CNS). People with impaired cellular immunity are at increased risk of developing severe measles but often cannot be vaccinated since the vaccine virus itself can lead to fatal illness in this population. There is no specific therapy for acute or persistent MeV manifestations. The only available intervention beside vaccination is hyperimmune sera from vaccinated individuals. The current vaccine elicits antibodies directed against the two envelope glycoproteins, the receptor-binding hemagglutinin and the fusion(F) protein. The antibodies against the hemagglutinin are neutralizing, while current-vaccine-elicited antibodies against the fusion protein are not. This contrasts with wild type induced immunity that elicits effective anti-F neutralizing antibodies. This indicates a clear shortcoming of the current vaccine (i.e., inability to elicit anti-F neutralizing antibodies) that affects the potency of hyperimmune sera obtained from vaccinated people. We have recently identified several anti-F neutralizing antibodies, and we propose to identify several others to build a defined cocktail of long-lasting monoclonal antibodies for future clinical application. The proposed work will address two Specific Aims: 1. Production and selection of anti-F neutralizing antibodies. 2. Evaluate the protection afforded by anti-F protein passive immunotherapy. Our application will significantly impact the growing number of severely immune- compromised individuals who cannot be vaccinated with the current live MeV vaccine and would benefit from a defined cocktail of neutralizing monoclonal antibodies. Project Number: 1R01AI195589-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Matteo Porotto (+1 co-PI) | Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY | Award Amount: $855,113 | Activity Code: R01 | Study Section: Drug Discovery and Molecular Pharmacology A Study Section [DMPA] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01AI19558901