Antibody responses of healthy adults to the p27 peptide of respiratory syncytial virus fusion protein

• Published in: Vaccine Vol. 40; no. 3; pp. 536 - 543
• Main Authors: Blunck, Brittani N., Aideyan, Letisha, Ye, Xunyan, Avadhanula, Vasanthi, Ferlic-Stark, Laura, Zechiedrich, Lynn, Gilbert, Brian E., Piedra, Pedro A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 24-01-2022; Elsevier Limited
• Subjects: Adult; Adults; Amino acids; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; Antibody response; Antigens; Child; Child, Preschool; Children; F protein; Furin; Furin cleavage site; Fusion protein; Health care; Humans; Immunization; Immunoassays; Immunoglobulin A; Immunoglobulin G; Infections; Laboratories; Monoclonal antibodies; Neutralizing; P27 peptide; Peptides; Pneumovirus; Post-translation; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccines; Viral Fusion Proteins; Viral infections; Virions; Viruses; Furin cleavage site; Respiratory syncytial virus; P27 peptide; Fusion protein; Pneumovirus
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.11.087

•Serum p27 antibody was measured following natural RSV infection in healthy adults.•Anti-p27 antibodies were detected in all healthy adults at all study visits.•Antibodies to the p27 region are generated following natural RSV reinfection.•p27 is not an immunodominant epitope in healthy adults.•Serum IgG anti-RSV/B p27 antibody titers were lower than IgG anti-RSV/A p27 titers.
The respiratory syncytial virus (RSV) fusion (F) protein undergoes two furin-cleavage events to become fusion competent, resulting in the release of a twenty-seven amino acid peptide (p27). Recent studies indicate that the p27 region of the F protein was an immunodominant antigen in young children. In this study, we evaluated the kinetics of the serum antibody response to the p27 peptide following natural RSV reinfection in adults. Nineteen healthy adults under sixty-five years of age were enrolled during the 2018–2019 RSV season in Houston, TX. Blood was collected at three study visits and RSV infection status was defined by changes in neutralizing antibody resulting in three groups: uninfected (n = 12), acutely infected (n = 4), and recently infected (n = 3). Serum IgG and IgA antibodies against RSV/A and RSV/B p27 peptides were measured by enzyme-linked immunosorbent assays, and serum p27-like antibodies were detected by a p27 competitive antibody assay. Anti-p27 antibodies were detected in all subjects at each study visit. The measured IgG and IgA anti-p27 antibody levels followed the same pattern as other RSV site-specific and neutralizing antibody responses described for this cohort previously: the uninfected group had stable responses for the duration of the study period, the acutely infected group had a significant increase following RSV infection, and the recently infected group had a decrease in anti-p27 antibody during the study period. These results indicate that antibodies to the p27 region of the F protein are generated following natural RSV reinfection and suggest that some of the F protein is potentially in a partially cleaved state on the surface of virions, expanding on the previous assumption that all of p27 is post-translationally released and not present on mature F. Additionally, antibody responses were significantly lower (1.4–1.5-fold) toward RSV/B than to RSV/A p27 at each study visit, despite being an RSV/B dominant outbreak. Understanding the mechanism for the differences in the magnitude of the RSV/A and RSV/B p27 antibody response may enhance our understanding of the intracellular processing of the F protein.