Vaccines and monoclonal antibodies have recently become available to prevent and treat respiratory syncytial virus (RSV) infections, a leading cause of hospitalization among infants and older people with chronic health conditions.
Yet there are no approved vaccines or treatments for equally dangerous infections caused by a close relative, the human metapneumovirus (hMPV). While uncommon, variants of RSV that can evade current vaccines and therapeutic antibodies have been reported.
Now researchers at Vanderbilt Health have identified five human antibodies that are cross-reactive for both RSV and hMPV. One of the antibodies, RM 5-1, provided protection against both viruses in a mouse challenge model, the researchers reported Jan. 16 in the journal Cell Reports Medicine.
The single administration of an antibody that provides cross-protection against both RSV and hMPV infection could provide logistical and economic advantages over the need to develop and administer multiple virus-specific monoclonal antibodies, the researchers noted.
“A single monoclonal antibody providing effective protection against both of these clinically important pathogens will be highly significant, especially for vulnerable populations,” said Ivelin Georgiev, PhD, director of the Vanderbilt Program in Computational Microbiology and Immunology and the paper’s corresponding author.
Georgiev, the Louise B. McGavock Professor and professor of Pathology, Microbiology and Immunology, is a leader in the use of computational approaches to advance disease treatment and prevention.
Several years ago, his team developed an antibody discovery tool called LIBRA-seq that has hastened the identification of ultrapotent and cross-reacting antibodies against multiple viruses, including those that cause COVID-19, AIDS and hepatitis C.
LIBRA-seq (Linking B-cell Receptor to Antigen Specificity through sequencing) enables researchers to map the unique sequence of amino acids that make up the reactive portion of an antibody and match it to the specificities of the antigen it targets simultaneously and in a high throughput way.
In the current study, LIBRA-seq identified five cross-reactive antibodies that showed high neutralization potencies against both RSV and hMPV. RM 5-1 potently neutralized all major RSV and hMPV subgroups, making it “an attractive target for further translational development,” the researchers concluded.
The paper’s first author, former Vanderbilt graduate student Alexandra Abu-Shmais, PhD, is a postdoctoral fellow at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Other Vanderbilt co-authors are Sabina Leonard, Alexis Janke, Matthew Vukovich, PhD, Lindsay Bass, Yukthi Suresh, Rachael Wolters, DVM, Nurgun Kose, Robert Carnahan, PhD, James Crowe Jr., MD, and Rachel Bonami, PhD.
The research was supported in part by NIH grants R01AI175245, T32AI112541, K01OD036063, T32AR059039, F31DK141224 and R01DK131070, and by the G. Harold and Leila Y. Mathers Charitable Foundation and the Welch Foundation.
