Predictors of survival after vaccination in a pneumonic plague model

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Moore, Barry D. and Macleod, Clair and Henning, Lisa and Krile, Richard and Chou, Y.L. and Laws, Tom R and Butcher, Wendy A and Moore, Kristoffer G and Walker, Nicola J and Williamson, E. Diane and Galloway, Darrell R (2022) Predictors of survival after vaccination in a pneumonic plague model. Vaccines, 10 (2). 145. ISSN 2076-393X (https://doi.org/10.3390/vaccines10020145)

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Abstract

Background: The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Methods: Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination. We varied vaccine type, as either a genetic fusion of the F1 and V protein antigens or a mixture of these two recombinant antigens, as well as antigen dose-level and formulation in order to correlate immune response to survival. Results: Whilst there was interaction between each of the variables of vaccine type, dose level and formulation and these all contributed to survival, vaccine formulation in protein-coated microcrystals (PCMCs) was the key contributor in inducing antibody titres. From these data, we propose a cut-off in total serum antibody titre to the F1 and V proteins of 100 µg/mL and 200 µg/mL, respectively. At these thresholds, survival is predicted in this murine pneumonic model to be >90%. Within the total titre of antibody to the V antigen, the neutralising antibody component correlated with dose level and was enhanced when the V antigen in free form was formulated in PCMCs. Antibody titre to F1 was limited by fusion to V, but this was compensated for by PCMC formulation. Conclusions: These data will enable clinical assessment of this and other candidate plague vaccines that utilise the same vaccine antigens by identifying a target antibody titre from murine models, which will guide the evaluation of clinical titres as serological surrogate markers of efficacy.

ORCID iDs

Moore, Barry D. ORCID logoORCID: https://orcid.org/0000-0002-4943-1632, Macleod, Clair ORCID logoORCID: https://orcid.org/0000-0001-7036-1790, Henning, Lisa, Krile, Richard, Chou, Y.L., Laws, Tom R, Butcher, Wendy A, Moore, Kristoffer G, Walker, Nicola J, Williamson, E. Diane and Galloway, Darrell R;
CORE (COnnecting REpositories)