Antibody Correlates of Protection From Severe Respiratory Syncytial Virus Disease in a Vaccine Efficacy Trial

Youyi Fong; Ying Huang; Bhavesh Borate; Lars W P van der Laan; Wenbo Zhang; Lindsay N Carpp; Iksung Cho; Greg Glenn; Louis Fries; Raphael Gottardo; Peter B Gilbert

doi:10.1093/ofid/ofac693

Antibody Correlates of Protection From Severe Respiratory Syncytial Virus Disease in a Vaccine Efficacy Trial

Open Forum Infect Dis. 2023 Jan 12;10(1):ofac693. doi: 10.1093/ofid/ofac693. eCollection 2023 Jan.

Authors

Youyi Fong^{1

2}, Ying Huang^{1

2}, Bhavesh Borate¹, Lars W P van der Laan¹, Wenbo Zhang¹, Lindsay N Carpp¹, Iksung Cho³, Greg Glenn³, Louis Fries³, Raphael Gottardo¹, Peter B Gilbert^{1

2

4}

Affiliations

¹ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
² Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
³ Novavax, Inc, Gaithersburg, Maryland, USA.
⁴ Department of Biostatistics, University of Washington, Seattle, Washington, USA.

Abstract

Background: Respiratory syncytial virus (RSV) can cause serious lung infections in young children and there is currently no available vaccine.

Methods: We used complementary statistical frameworks to analyze 4 RSV serology measurements in mothers and their infants in South Africa who participated in a phase 3 maternal immunization trial of an RSV F protein nanoparticle vaccine as correlates of risk and of protection against different RSV disease endpoints.

Results: We found evidence to support each antibody measurement-encompassing RSV-neutralizing antibodies and F surface glycoprotein-binding antibodies-as an inverse correlate of risk of RSV-associated acute lower respiratory tract infection with severe hypoxia in at least 1 framework, with vaccine-induced fold-rise from the maternal enrollment to day 14 samples of anti-F immunoglobulin G (IgG) binding antibodies having the most consistent evidence. This evidence includes a significant association of fold-rise anti-F IgG with vaccine efficacy (VE); achieving a baseline covariate-adjusted VE of 75% requires a vaccine-induced maternal anti-F IgG fold-rise of around 16. Neither multivariable logistic regression nor superlearning analyses showed benefit to including multiple time points or assays in the same model, suggesting a parsimonious correlate. Post hoc exploratory analyses supported adherence of vaccine-induced maternal anti-F IgG fold-rise to the Prentice criteria for a valid surrogate endpoint.

Conclusions: Our results suggest that the vaccine induced protective anti-F antibody responses. If this finding is confirmed, VE could potentially be augmented by increasing these responses.

Keywords: F glycoprotein; Prentice criteria surrogate endpoint; nonparametric threshold regression; principal stratification causal inference; superlearning.

Abstract

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