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Vaccine. 2018 Sep 25;36(40):5967-5976. doi: 10.1016/j.vaccine.2018.08.059. Epub 2018 Aug 29.

Thermal stability and epitope integrity of a lyophilized ricin toxin subunit vaccine.

Author information

1
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, United States.
2
Soligenix, Inc., Princeton, NJ 08540, United States.
3
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, United States. Electronic address: nicholas.mantis@health.ny.gov.

Abstract

Biodefense vaccine are destined to be stockpiled for periods of time and deployed in the event of a public health emergency. In this report, we compared the potency of liquid and lyophilized (thermostabilized) formulations of a candidate ricin toxin subunit vaccine, RiVax, adsorbed to aluminum salts adjuvant, over a 12-month period. The liquid and lyophilized formulations were stored at stressed (40 °C) and unstressed (4 °C) conditions and evaluated at 3, 6 and 12-month time points for potency in a mouse model of lethal dose ricin challenge. At the same time points, the vaccine formulations were interrogated in vitro by competition ELISA for conformational integrity using a panel of three monoclonal antibodies (mAbs), PB10, WECB2, and SyH7, directed against known immunodominant toxin-neutralizing epitopes on RiVax. We found that the liquid vaccine under stress conditions declined precipitously within the first three months, as evidenced by a reduction in in vivo potency and concomitant loss of mAb recognition in vitro. In contrast, the lyophilized RiVax vaccine retained in vivo potency and conformational integrity for up to one year at 4 °C and 40 °C. We discuss the utility of monitoring the integrity of one or more toxin-neutralizing epitopes on RiVax as a possible supplement to animal studies to assess vaccine potency.

KEYWORDS:

B cell epitope; Biodefense; Monoclonal antibodies; Toxin; Vaccine

PMID:
30172637
PMCID:
PMC6320669
[Available on 2019-09-25]
DOI:
10.1016/j.vaccine.2018.08.059
[Indexed for MEDLINE]

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