Improved Immune Responses in The Elderly
An LT-IS patch was also tested in humans vaccinated with a commercial influenza vaccine.15 In this clinical study, three groups of approximately 55 volunteers were vaccinated with a standard injected flu vaccine
consisting of A/New Caledonia, A/Panama, and B/Shangdong. The first group consisted of healthy young adults; the second and
third groups consisted of elderly adults over 65 years of age. In the third group, the elderly subjects were vaccinated with
the flu vaccine in combination with the LT-IS patch (50 μg LT). Three weeks following the vaccination, the hemagglutination
inhibition (HAI) responses were measured. Figure 4 shows the percentage of seroconversion based on a four-fold rise in HAI
titers. The percent change in seroconversion was highest for the healthy young adults (first group), followed by the elderly
group (third group) receiving the LT-IS patch. Overall, the LT-IS patch improved the elderly seroconversion rates by 23%,
18%, and 12% percentage points for A/New Caledonia, A/Panama, and B/Shangdong, respectively, as compared to the second group
which received the vaccination alone. This study shows that an LT-IS patch applied onto the skin after an IM injection can
augment the immune response, as predicted from animal models.
Figure 4. Seroconversion rates of patients in a human clinical trial testing IS patch performance in elderly. Young adults
had 69%, 56%, and 61% seroconversion rates for A/New Caledonia, A/Panama and B/Shandong respectively. These rates were significantly
higher or showed a trend compared to corresponding seroconversion rates in the elderly without a patch (40% [p=0.005], 36%
[p=0.06], and 38% [p=0.03], respectively). The addition of an IS patch to the elderly improved these seroconversion rates
to 63%, 54%, and 50% respectively, reaching significance in the A/New Caledonia strain (p=0.01) and a trend for A/Panama (p=0.08).
The seroconversion rates in elderly receiving the patch were not significantly different from those in healthy adults, and
represent an absolute improvement of 23% (A/New Caledonia), 18% (A/Panama) and 12% (B/Shandong) in seroconversion of the elderly
over those not receiving the patch.
Wet Versus Dry Patch Formulations
The preclinical and Phase 1 studies used the LT-IS patch in a wet patch format. A dry patch offers advantages over a wet patch
in terms of ease of use in a clinical setting (i.e., fewer manipulative steps required for administration), commercial viability
(i.e., production, packaging, and distribution), and stability (i.e., dry product is expected to be more stable than liquid
product due to removal of bulk water). Recently, we developed a stable formulation matrix and process technology to compound
adjuvants, as well as vaccine antigens of interest, into a dry patch format. Using this formulation platform technology, we
have prepared a dry formulated LT patch and have conducted a clinical trial to compare the effect of a wet versus dry LT patch
on skin delivery.