We also present real-time stability data showing that the dry LT-IS patch is stable at 2–8 °C for at least 22 months. Based
on accelerated and thermal cycling stress data, the dry LT-IS patch has an adequate thermostability profile to allow storage
and use at room temperature and to withstand extreme temperatures during shipment and distribution.
A pilot-scale manufacturing operation has been custom-built specifically for making LT and other vaccine-based patches. Scale-up
work is currently under way to produce and stockpile 150 million LT-IS patches.
Preclinical and Clinical Studies
Dose Sparing for Bird Flu Vaccine Candidate
In a mouse study, the LT-IS patch provided up to 100-fold dose sparing for a pandemic flu vaccine candidate (Figure 1). For
this study, three groups of mice were immunized intradermally (ID) with a recombinant hemagglutinin (rHA) protein representing
the A/Vietnam/1203/2004 (H5N1) strain at 1.5 μg, 0.15 μg, and 0.015 μg. Half of each group had an LT-IS patch (containing
10 μg LT) placed over the injection site and the other half received a placebo (no LT) patch. Following a two-dose regimen
at Day 0 and Day 14, the rHA immune responses were determined two weeks after the second dose. As indicated in Figure 1, the
group receiving the 0.015 μg dose with the LT-IS patch had an antibody response (47,491 ELISA units) comparable to the group
receiving the 1.5 μg dose ID alone (20,142). This data suggests that a 100-fold reduction in vaccine may be achieved when
the vaccine is delivered intradermally with the LT-IS patch. Data collected in the same study suggests that a 10-fold reduction
in vaccine can be achieved when the vaccine is delivered by intramuscular injection (IM) (data not shown).
Figure 1. Dose sparing in the mouse model using rH5 (Anti-A/Vietnam/1203/2004). Mice received two intradermal immunizations
14 days apart of 0.015, 0.15, or 1.5 μg rHA and IS patches containing either 10 μg LT or a placebo with no LT. Serum IgG titers
were determined by an ELISA method. Results of individual animals (open circles) and the group geomeans (bars) are shown.
Groups receiving LT have statistically greater titers than groups receiving placebo patches.