Predictors of Survival after Vaccination in a Pneumonic Plague Model

Vaccines

Lisa Henning¹  Robert Krile¹  Ying-Liang Chou¹  Thomas R. Laws²  Wendy A. Butcher²  Nicola J. Walker²  Ethel Diane Williamson²  Kristoffer M. Moore²  Darrell R. Galloway³  Clair Macleod⁴  Barry D. Moore⁴ 

[1] Battelle Biomedical Research Center, West Jefferson, OH 43162, USA;CBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UK;Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA;Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XQ, UK;

关键词: plague;    vaccine;    formulation;    immunity;    correlates;   

DOI  :  10.3390/vaccines10020145

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown