Pre-vaccination frequency of circulatory Tfh is associated with robust immune response to TV003 dengue vaccine

• Type of Material: Article
• Authors: Abdullah M Izmirly, King Abdulaziz University; Adam N Pelletier, RPM Bioinfo Solutions; Jennifer Connors, Drexel University College of Medicine; Bhavani Taramangalam, Drexel University College of Medicine; Sawsan O Alturki, King Abdulaziz University; Emma A Gordon, Drexel University College of Medicine; Sana O Alturki, King Abdulaziz University; Joshua C Mell, Drexel University College of Medicine; Gokul Swaminathan, Drexel University College of Medicine; Vivin Karthik, Drexel University College of Medicine; Michele A Kutzler, Drexel University College of Medicine; Esper G Kallas, Universidade de São Paulo; Rafick-Pierre Sekaly, Emory University; Elias K Haddad, Drexel University College of Medicine
• Language: English
• Date: 2022-01-01
• Publisher: PLOS
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Izmirly et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1009903
• Title of Journal or Parent Work: PLoS Pathogens
• Volume: 18
• Issue: 1
• Start Page: e1009903
• End Page: e1009903
• Grant/Funding Information: This work was supported with funds from NIH RO1 AI125202 to RPS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Immunogenicity, Vaccine; Dengue; Vaccines, Combined; Antibodies, Viral; Dengue Vaccines; Antibodies, Neutralizing; T Follicular Helper Cells; Female; Male; Humans
• Research Categories: Health Sciences, Pathology

Abstract

It has been estimated that more than 390 million people are infected with Dengue virus every year; around 96 millions of these infections result in clinical pathologies. To date, there is only one licensed viral vector-based Dengue virus vaccine CYD-TDV approved for use in dengue endemic areas. While initially approved for administration independent of serostatus, the current guidance only recommends the use of this vaccine for seropositive individuals. Therefore, there is a critical need for investigating the influence of Dengue virus serostatus and immunological mechanisms that influence vaccine outcome. Here, we provide comprehensive evaluation of sero-status and host immune factors that correlate with robust immune responses to a Dengue virus vector based tetravalent vaccine (TV003) in a Phase II clinical cohort of human participants. We observed that sero-positive individuals demonstrate a much stronger immune response to the TV003 vaccine. Our multi-layered immune profiling revealed that sero-positive subjects have increased baseline/pre-vaccination frequencies of circulating T follicular helper (cTfh) cells and the Tfh related chemokine CXCL13/BLC. Importantly, this baseline/pre-vaccination cTfh profile correlated with the vaccinees’ ability to launch neutralizing antibody response against all four sero-types of Dengue virus, an important endpoint for Dengue vaccine clinical trials. Overall, we provide novel insights into the favorable cTfh related immune status that persists in Dengue virus seropositive individuals that correlate with their ability to mount robust vaccine specific immune responses. Such detailed interrogation of cTfh cell biology in the context of clinical vaccinology will help uncover mechanisms and targets for favorable immuno-modulatory agents.