Journal of Vaccines & Vaccination

Activation of protective innate-adaptive immunity duo for conferring rapid-sustained-broad protection of vaccines against infectious agents

5^th Asia Pacific Global Summit and Expo on Vaccines & Vaccination

July 27-29, 2015 Brisbane, Australia

De-chu Christopher Tang

Posters-Accepted Abstracts: J Vaccines Vaccin

Abstract:

We report that intranasal administration of an E1/E3-defective (?E1E3) adenovirus serotype 5 (Ad5)-vectored influenza vaccine could induce seroconversion in human volunteers without appreciable adverse effects, even in subjects with preexisting Ad5 immunity. Mice and ferrets were well protected against challenge by a lethal dose of an H5N1 avian influenza virus following intranasal instillation of an Ad5 vector encoding hemagglutinin (HA) in a single-dose regimen. Moreover, the ?E1E3 Ad5 particle itself without transgene could confer rapid-sustained-broad protection against influenza by inducing an anti-influenza state in a drug-like manner, conceivably by activating a specific arm of innate immunity. An Ad5 vector encoding HA thus consolidates drug and vaccine into a single package, which allows the Ad5 backbone to induce protective innate immunity capable of conferring nearly-immediate and prolonged (e.g., 5 hours to 47 days) protection as the first wave against influenza; followed by HA-mediated adaptive immunity as the second wave before the innate immunity-associated anti-influenza state declines away. In addition to ?E1E3 Ad5?s capacity to rapidly induce an anti-influenza state, an Ad5 vector encoding a bioengineered Bacillus anthracis protective antigen (PA) could also confer rapid (e.g., 1-2 days) prophylactic or post-exposure anthrax therapy with synergy to antibiotic treatment in a murine model. Both rabbits and macaques were well protected by an Ad5-PA-vectored nasal anthrax vaccine in a single-dose regimen against inhalational anthrax following challenge with a lethal dose of Bacillus anthracis Ames spores. Overall, the work conceivably would foster the development of a novel noninvasive drugvaccine duo platform technology capable of conferring rapid-sustained-broad protection against pathogens with neither the potential to induce drug resistance nor that to trigger harmful systemic inflammation.