Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses
Figure 6
Kinetics of protection after single-dose rAd immunization.
BALB/cAnNCr mice were immunized with 5×109 particles each of A/NP-rAd and M2-rAd, or 1×1010 particles of B/NP-rAd i.n. or i.m. and challenged with 104 TCID50 (∼100 LD50) of A/FM at 1, 2, 3, or 4 weeks or 6 months later. Left panels show survival and right panels show weight loss after challenge. Groups consisted of 10 mice per immunization per challenge time. Error bars in weight loss graphs indicate mean ± SEM. Statistically significant (P<0.05) differences in survival were as follows: A/NP+M2-rAd i.n. was significantly different from A/NP+M2-rAd i.m. at weeks 2, 3, and 4, and from B/NP-rAd i.n. or i.m. at all times; A/NP+M2-rAd i.m. was significantly different from B/NP-rAd i.m. at 2 weeks and 6 months, but not different from B/NP-rAd i.n. at any time. In terms of weight loss, no statistically significant differences were seen between groups at week 1. At week 2 A/NP+M2-rAd i.n. differed (P<0.05) from all other groups on days 2–7, and also from B/NP-rAd i.n. on day 1; A/NP+M2-rAd i.m. was significantly different from B/NP-rAd i.n. on days 2–3 and from B/NP-rAd i.m. on day 1. At week 3 A/NP+M2-rAd differed from all other groups on days 2–8; B/NP-rAd i.n. differed from all other groups on day 3. At week 4 A/NP+M2-rAd i.n. was significantly different from all other groups on days 2–15; A/NP+M2-rAd i.m. differed from B/NP-rAd i.m. on day 11. At 6 months A/NP+M2-rAd i.n. was significantly different from all other groups on days 2–10, and from A/NP+M2-rAd i.m. on days 11–15.