Respiratory syncytial virus (RSV) vaccine effectiveness and antibody correlates of protection among older adults in the Community Vaccine Effectiveness (CoVE) observational study

Abstract

Background: The first RSV vaccines for adults 60 years and older were approved prior to the 2023-2024 respiratory virus season. This study aims to evaluate RSV vaccine effectiveness (VE) in preventing RSV infections among older adults, and to examine antibody correlates of protection.

Methods: This study used data from adults 60 years and older, enrolled into the Community Vaccine Effectiveness (CoVE) prospective cohort study, in Michigan, U.S.A. A Cox regression model was used to compare incidence of symptomatic/all RSV infections in those vaccinated versus unvaccinated. RSV-specific (preF) binding antibodies were measured in serum specimens and assessed longitudinally. A correlates of protection analysis was conducted using logistic regression.

Findings: Of the 281 participants (n = 117 vaccinated) enrolled (August 1, 2023, to March 1, 2024), 14 tested positive for RSV. Adjusted RSV VE against any RSV infection was 50.8% (95% CI: -79.1% to 86.5%), and 59.8% (95% CI: -105.2% to 92.1%) against symptomatic RSV. There were 61.2 (95% CI: 16.9, 163.2) RSV infections per 1000 person-years among participants who were vaccinated compared to 165.8 infections (95% CI: 88.0, 287.0) per 1000 person-years among those unvaccinated. A 31% decrease in odds (OR: 0.69, 95% CI: 0.44-1.07) of RSV infection per 2-fold increase in antibody concentration was observed.

Interpretation: Our findings suggest that higher antibody levels may be associated with a reduced risk of RSV infection, but further research is needed to confirm this relationship. RSV incidence appeared to be lowest among adults who were vaccinated, though the difference was not statistically significant. Low number of RSV events and limited availability of serology data limit the precision of the estimates. Continued monitoring of reduction of RSV infection in years following vaccination is warranted.

Funding: National Center for Immunisation and Respiratory Diseases, U.S. Centers for Disease Control and Prevention (75D30122C13149) and National Institute of Allergy and Infectious Diseases (75N93021C00015). The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Keywords: Antibody waning; Cohort study; Correlates of protection; Older adults; Respiratory syncytial virus; Vaccine effectiveness.

Fig. 1

COVE RSV vaccinations (light grey) in adults 60 years of age and older, included in the analysis. All RT-PCR-confirmed RSV infections (dark grey) in all CoVE participants of any age during the 2023–2024 season are noted in green. ∗RSV among 994 participants enrolled in COVE. 112 RSV infections among 108 people (4 people with 2 infections). Median age 13.6 years (1–83). RSV: Respiratory Syncytial Virus. RT-PCR: Real-Time Polymerase Chain Reaction.

Fig. 2

Relationship between measured antibody concentrations against pre-fusion RSV F protein and RSV infection risk. The number of subjects within each interval is plotted on the left y-axis, and the proportion of subjects who were infected with RSV is plotted on the right y-axis, with the red line denoting the proportion infected. RSV: Respiratory Syncytial Virus. AU/ml: Arbitrary Units per ml.

Fig. 3

Spaghetti plots of longitudinal changes in RSV preF IgG concentrations over time. The time scale on the left panel (unvaccinated group) corresponds to the time since the start of the study period (derived from the timing between August 1, 2023, and sample collection date). The time scale on the right panel (vaccinated group) is time since RSV vaccination (derived from the timing between RSV vaccination date and sample collection date). A loess curve was added to each panel to examine the overall trend. N = number of individuals. RSV: Respiratory Syncytial Virus.

Fig. 4

Predicted trajectories of RSV preF IgG levels over time using ED (Exponential Decay), PL (Power-Law), and NCS (Natural Cubic Splines) mixed models. Dots on both panels represent the original data points on a log10 scale. The vertical dashed lines represent the location of the two inner knots from the NCS mixed models. RSV: Respiratory Syncytial Virus.