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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Bivalent RSV prefusion F vaccination elicits effective neutralization of contemporary and monoclonal
Wei Chen1, Lyndsey T Martinez1, Larissa Falcao1
1Vaccines, Pfizer Inc, Pearl River, NY, USA.
Insights
The bivalent Respiratory Syncytial Virus prefusion F protein (RSVpreF) vaccine elicits a strong immune response. This response effectively neutralizes diverse circulating RSV strains and monoclonal antibody-resistant variants, offering broad protection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Respiratory Syncytial Virus (RSV) causes significant infant and older adult respiratory illness.
- The RSV prefusion F protein (preF) is a key target for neutralizing antibodies and vaccine development.
- The bivalent RSVpreF vaccine (Abrysvo®) targets both RSV A and B subgroups using stabilized preF antigens.
Purpose of the Study:
- To characterize the neutralizing activity of human immune sera from the RSVpreF vaccine.
- To assess neutralization against contemporary, globally circulating RSV A and B clinical isolates.
- To evaluate neutralization against monoclonal antibody-resistant mutant strains (MARMs).
Main Methods:
- Characterization of neutralizing activity of adult RSVpreF immune sera.
- Testing against a panel of 65 global RSV A and B clinical isolates with antigenic site variations.
- Evaluation of monoclonal antibody-resistant mutant strains (MARMs) with high-level in vitro resistance.
Main Results:
- RSVpreF immune sera demonstrated effective neutralization of all tested global clinical isolates.
- The vaccine-induced polyclonal response effectively neutralized all tested MARMs, including those resistant to nirsevimab, clesrovimab, and palivizumab.
- Robust neutralizing activity was observed against both RSV A and B strains.
Conclusions:
- The bivalent RSVpreF vaccine induces a polyclonal immune response with broad neutralizing activity.
- This response is effective against currently circulating RSV strains, including those with resistance mutations.
- The vaccine provides broad protective immunity against RSV disease.
Abstract:
Respiratory syncytial virus (RSV) is the leading global cause of serious respiratory disease in infants and an important respiratory pathogen in older adults. The RSV prefusion F protein (preF) is a major target of neutralizing antibodies shown to protect against RSV disease. The bivalent preF protein subunit vaccine (RSVpreF; Abrysvo®) contains stabilized preF antigens representing the two major RSV subgroups, RSV A and RSV B. Here, we characterized the neutralizing activity of adult RSVpreF immune sera against a panel of 65 contemporary, globally circulating RSV A and RSV B clinical isolates, containing various amino acid substitutions across the five major antigenic sites of RSV F (Ø, I, II, III, V). Monoclonal Ab-resistant mutant strains (MARMs) displaying in vitro resistance to nirsevimab, clesrovimab, and palivizumab (up to 300,000-fold resistance over the parental strain) were also evaluated. RSVpreF immune sera effectively neutralized both the panel of global clinical isolates and all MARMs tested. These findings demonstrate that the bivalent RSVpreF polyclonal response maintains robust neutralizing activity against circulating RSV A and B strains, including those that escape RSV F mAbs, and provides broad protective immunity against RSV.

