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. 2021 Feb 22;39(8):1248-1256.
doi: 10.1016/j.vaccine.2021.01.045. Epub 2021 Jan 26.

A prospective surveillance study on the kinetics of the humoral immune response to the respiratory syncytial virus fusion protein in adults in Houston, Texas

Brittani N Blunck  1 , Letisha Aideyan  1 , Xunyan Ye  1 , Vasanthi Avadhanula  1 , Laura Ferlic-Stark  1 , Lynn Zechiedrich  2 , Brian E Gilbert  1 , Pedro A Piedra  3
Affiliations

A prospective surveillance study on the kinetics of the humoral immune response to the respiratory syncytial virus fusion protein in adults in Houston, Texas

Brittani N Blunck et al. Vaccine. .

Abstract

Respiratory syncytial virus (RSV)-specific serum antibody has been correlated to protection of infection and reduction of severe disease, but reinfection is still frequent. In this study, we evaluated RSV-specific serum antibody activity following natural RSV re-infection to examine the longevity of the humoral immune response in adults. Nineteen healthy adult volunteers under sixty-five years of age were enrolled during the 2018-2019 RSV season in Houston, TX. Blood was collected at three study visits. The kinetics of RSV-neutralizing, RSV F site-specific competitive, and RSV-binding antibodies in serum samples were measured by microneutralization and enzyme-linked immunosorbent assays. Three distinct profiles of RSV-specific antibody kinetics were identified that were consistent with RSV infection status: uninfected, acutely infected, and recently infected. The uninfected group had stable antibody titers for the duration of the study period (185 days). The acutely infected group had lower antibody responses at the beginning of the study, supporting a correlate of infection, followed by a significant antibody response after infection that was maintained for at least 125 days. Unlike the acutely infected group, the recently infected group had a significant precipitous decrease in RSV antibody in only 60 days. This study is the first, to our knowledge, to describe this abrupt loss of RSV-specific antibody in detail. This rapid decline of antibody may present an obstacle for the development of vaccines with lasting protection against RSV, and perhaps other respiratory pathogens. Neutralizing antibody responses were greater to prototypic than contemporaneous RSV strains, regardless of infection status, indicating that original antigenic sin may impact the humoral immune response to new or emerging RSV strains.

Keywords: Binding antibody; Competitive antibody; Neutralizing antibody; Original antigenic sin; Respiratory viruses; Vaccine.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig 1.
Fig 1.. Sampling times during the 2018–2019 RSV season.
Healthy adult volunteers were enrolled in a prospective, observational surveillance study during the 2018–2019 RSV season. Blood was collected at three study visits (shaded boxes) during the early RSV season, after peak RSV season, and late RSV season, based upon RSV surveillance data from Texas Children’s Hospital in Houston, TX, USA. The season is shown by CDC weeks.
Fig 2.
Fig 2.. Kinetics of RSV neutralizing antibody titers of individual study participants.
Neutralizing antibody titer was measured by microneutralization assays to prototypic (RSV/B/18537 and RSV/A/Tracy) and contemporaneous (RSV/B/Buenos Aires and RSV/A/Ontario) RSV strains at three study visits over the course of the 2018–2019 RSV season by infection status. Infection status includes: uninfected (n = 12), acutely infected (n = 4), and recently infected (n = 3). Neutralizing antibody is expressed in log2. The lower limit of detection is 2.5 log2. Each line represents one subject. Significant pairwise comparisons in post-estimated GMNAT (shown in Supplemental Table 2) between visits within each group are indicated as: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
Fig 3.
Fig 3.. Site-specific competitive antibody responses.
Four antigenic site-specific competitive antibody assays were used to measure serum concentrations of antibody that compete with biotinylated mAbs for binding to their respective antigenic site on the RSV fusion protein as described previously,. Monoclonal antibodies used include: D25 (site Ø), 131–2A (site I), palivizumab (site II), and 101F (site IV). Shown are (A) total geometric mean concentrations (CA-GMC), or (B) percent of each RSV antigenic site-specific CA-GMC (μg/mL) to the total CA-GMC (μg/mL) responses by infection status. Infection status includes: uninfected (n = 12), acutely infected (n = 4), and recently infected (n = 3). Significant pairwise comparisons in post-estimated CA-GMC of each group are indicated (*P ≤ 0.05).
Fig 4.
Fig 4.. Correlation of RSV antigenic site-specific competitive antibody concentrations and neutralizing antibody titers to RSV/B/18537 at study visits 1 and 2.
Pearson’s correlation coefficients were calculated to measure the strength of the linear association between the neutralizing antibody titer to RSV/B/18537 and competitive antibody concentrations to (A) site Ø, (B) site I, (C) site II, (D) site IV (n = 19). Significant correlations are indicated (*P ≤ 0.05, **P ≤ 0.01).
Fig 5.
Fig 5.. RSV-specific binding antibody to prefusogenic F protein.
The geometric mean concentration of the isotype composition (A) IgG, (B) IgA, and (C) IgM of RSV-specific binding antibodies present in serum samples was analyzed for responses against the prefusogenic form of the F protein (Novavax, Bethesda, MD) by infection status. Infection status includes: uninfected (n = 12), acutely infected (n = 4), and recently infected (n = 3). Significant differences in the geometric mean concentrations of each group are indicated (*P ≤ 0.05).
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