Vaccine-related major cutaneous reaction size correlates with cellular-mediated immune responses after tularaemia immunisation

• Authors: Rosangela Salerno-Goncalves, University of Maryland; Wilbur H Chen, University of Maryland; Mark Mulligan, Emory University; Sharon E Frey, St Louis University School of Medicine; Jack T Stapleton, University of Iowa, Iowa City; Wendy A Keitel, Baylor College of Medicine; Jason Bailey, Emmes, Rockville MD; Eli Sendra, Emmes, Rockville MD; Hill Hill, Emmes, Rockville MD; Robert A Johnson, Biomedical Advanced Research and Development Authority; Marcelo B Sztein, University of Maryland
• Journal Title: CLINICAL & TRANSLATIONAL IMMUNOLOGY
• Volume: Volume 10, Number 1
• Publisher: WILEY | 2021-01-01, Pages e1239-e1239
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/cti2.1239
• Subjects: Biology, Virology; Biology, Microbiology; Health Sciences, Oncology; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; human; T cells; take; tularaemia; vaccination; FRANCISELLA-TULARENSIS; T-CELLS; PROTECTIVE IMMUNITY; ADAPTIVE IMMUNITY; RECALL RESPONSES; RESIDENT MEMORY; WHITE-MOUSE; LIVE; STRAIN; SMALLPOX

Abstract

Objectives: Francisella tularensis, the causative agent of tularaemia, is an exceptionally infectious bacterium, potentially fatal for humans if left untreated and with the potential to be developed as a bioweapon. Both natural infection and live-attenuated vaccine strain (LVS) confer good protection against tularaemia. LVS vaccination is traditionally administered by scarification, and the formation of a cutaneous reaction or take at the vaccination site is recognised as a clinical correlate of protection. Although previous studies have suggested that high antibody titres following vaccination might serve as a useful surrogate marker, the immunological correlates of protection remain unknown. Methods: We investigated the host T-cell-mediated immune (T-CMI) responses elicited following immunisation with LVS vaccine formulated by the DynPort Vaccine Company (DVC-LVS) or the United States Army Medical Research Institute of Infectious Diseases (USAMRIID-LVS). We compared T-CMI responses prompted by these vaccines and correlated them with take size. Results: We found that both LVS vaccines elicited similar T-CMI responses. Interestingly, take size associated with the T cells’ ability to proliferate, secrete IFN-γ and mobilise degranulation, suggesting that these responses play an essential role in tularaemia protection. Conclusions: These results renew the appreciation for vaccination through the scarification as a prime route of inoculation to target pathogens driving specific T-CMI responses and provide further evidence that T-CMI plays a role in protection from tularaemia.