RSV Vaccine Effectiveness, HMPV Antibody, and MPO Biomarker Highlight Respiratory Virus Advances

New research reports strong real-world effectiveness for a bivalent RSV prefusion F vaccine, a potent monoclonal antibody against human metapneumovirus (HMPV), and a potential biomarker for RSV disease severity.

Real-world data on the bivalent RSV prefusion F vaccine from a multicenter, test-negative case-control study conducted at 14 hospitals in England showed high protection among people admitted with acute respiratory infection. The vaccine provided 78.8% protection against hospitalization for exacerbations of chronic lung disease, heart disease, or frailty, 86.7% effectiveness against severe RSV disease requiring oxygen, intensive care, or mechanical ventilation, 72.8% efficacy in immunocompromised individuals, and 82.3% efficacy in preventing hospitalization for RSV-associated acute respiratory infection.

RSV remains the major cause of acute lower respiratory infections worldwide, with an estimated 33 million new cases and over 3 million hospitalizations in children under five each year, and about 118,000 pediatric deaths annually, the majority occurring in low- and middle-income countries. Global circulation is driven by distinct viral lineages: the A.D.3 lineage has progressively increased in prevalence among RSV subtype A since 2022, while the B.D.E.1 lineage has dominated RSV subtype B circulation since 2023.

Following regulatory clearance of numerous first-generation RSV vaccines, clinical research has shifted to improving immunogenicity, assessing revaccination durability, and developing combination respiratory vaccines. Clover Biopharmaceuticals is developing SCB-1019, a recombinant RSV preF subunit vaccine that showed potential as an effective revaccination booster for older persons in Phase 1 findings, and has launched Phase 2 trials for combination candidates SCB-1022 (RSV + hMPV) and SCB-1033 (RSV + hMPV + PIV3). Moderna is conducting Phase 1 studies of mRNA-1365, a combination vaccine targeting RSV and hMPV in a single dose. The PIPELINE-RSV Trial, a multinational adaptive platform, is randomly assigning pregnant women and their infants to receive a maternal RSV vaccine, an infant monoclonal antibody, or both simultaneously.

In human metapneumovirus research, investigators described 4F11, a highly potent neutralizing monoclonal antibody with in vitro and in vivo efficacy against HMPV. Cryo-electron microscopy showed that 4F11 targets an epitope at the apex of the prefusion F protein (site Ø) with a 1:1 stoichiometry of Fab to trimer, distinct from the 3:1 stoichiometry of other site Ø antibodies. It binds vertically and directly interacts with the Asn172 glycan. The antibody showed high neutralization potency across diverse HMPV strains and a low propensity for resistance, with only a single escape mutation (K179E) identified that has not been found in any published HMPV sequence. In male hamsters, 4F11 significantly reduced viral loads in the lungs and nasal turbinates.

A separate study investigated neutrophil myeloperoxidase (MPO) as a functional biomarker for RSV severity. Peripheral blood neutrophils from infants with severe RSV disease admitted to the pediatric intensive care unit showed elevated MPO compared to age-matched controls. Using an air-liquid interface model incorporating pediatric airway epithelial cells, endothelial cells, and neutrophils, researchers found that both the antivirals remdesivir and RSV604 reduced viral load, but only RSV604 attenuated MPO expression. The findings suggest MPO could serve as a readout of therapeutic efficacy and that targeting neutrophil-driven inflammatory pathways may be critical for reducing pathology in infant RSV infection.