An Adenovirus-Based Vaccine with a Double-Stranded RNA Adjuvant Protects Mice and Ferrets against H5N1 Avian Influenza in Oral Delivery Models

Abstract

An oral gene-based avian influenza vaccine would allow rapid development and simplified distribution, but efficacy has previously been difficult to achieve by the oral route. This study assessed protection against avian influenza virus challenge using a chimeric adenovirus vector expressing hemagglutinin and a double-stranded RNA adjuvant. Immunized ferrets and mice were protected upon lethal challenge. Further, ferrets immunized by the peroral route induced cross-clade neutralizing antibodies, and the antibodies were selective against hemagglutinin, not the vector. Similarly, experiments in mice demonstrated selective immune responses against HA with peroral delivery and the ability to circumvent preexisting vector immunity.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

“…We have also tested delivery of vaccines and drugs to ex vivo pig skin with these silicon microneedles3334 using accepted models of transcutaneous drug delivery; this gives us an initial level of confidence that these silicon microneedle patches will deliver vaccine in vivo to humans. Furthermore, we63536 and others1137 have also previously demonstrated that immunogenicity findings in mice for adenovirus-based vaccines can translate to humans. However, in the absence of clinical testing, we cannot predict if adenovirus-based vaccine administration using solid microneedle patches would result in the same effect on immunogenicity and protection in humans as was determined in this study.…”

Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial

“…Fecal IgA responses were still elevated 6 months after immunization. In addition, there was no evidence that preexisting immunity to the recombinant Ad5 (rAd5) vector affected the ability to elicit a norovirus-specific immune response (see Supplemental Methods), which has been demonstrated in additional indications and studies using the same oral vaccine platform (17,27).…”

“…The vector also encodes a molecular dsRNA hairpin adjuvant driven by a separate promoter. Details of the rAd vector platform have been described previously (27). GMP drug substance was produced in HyClone Single Use Bioreactors (GE Healthcare Life Sciences) at Lonza Biologicals.…”

Ebola virus disease candidate vaccines under evaluation in clinical trials

“…Oral administration of a live adenovirus-vectored vaccine abrogates the relevance of pre-existing vector immunity, resulting in a robust immune response to the delivered antigen [42,43,70,71]. The US company Vaxart, which is currently evaluating an oral adenovirus-based influenza vaccine in a Phase I clinical trial (NCT02547792), has also developed an oral adenovirus-based EVD vaccine with plans to enter clinical trials.…”