Adenovirus-vectored drug–vaccine duo as a potential driver for conferring mass protection against infectious diseases

Abstract

The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its power by boosting vaccine coverage requires the development of a new generation of rapid-response vaccines that can be mass produced at low costs and mass administered by nonmedical personnel. The new vaccines also have to be endowed with a higher safety margin than that of conventional vaccines. The nonreplicating adenovirus-vectored vaccine holds promise in boosting vaccine coverage because the vector can be rapidly manufactured in serum-free suspension cells in response to a surge in demand, and noninvasively administered by nasal spray into human subjects in compliance with evolutionary medicine. In contrast to parenteral injection, noninvasive mucosal vaccination minimizes systemic inflammation. Moreover, pre-existing adenovirus immunity does not interfere appreciably with the potency of an adenovirus-vectored nasal vaccine. Nasal administration of adenovirus vectors encoding pathogen antigens is not only fear-free and painless, but also confers rapid and sustained protection against mucosal pathogens as a drug–vaccine duo since adenovirus particles alone without transgene expression can induce an anti-influenza state in the airway. In addition to human vaccination, animals can also be mass immunized by this class of vectored vaccines.

Keywords::

• adenovirus
• drug resistance
• drug–vaccine duo
• influenza therapy
• mass immunization
• nasal vaccine
• safety
• vaccine

Acknowledgements

The authors thank the University of Alabama at Birmingham for providing the animal facility and performing a human clinical trial of an adenovirus-vectored avian influenza (H5N1) vaccine; Southern Research Institute for performing some of the assays and animal challenge studies in their BSL-3⁺ facility; Southeast Poultry Research Laboratory for challenging chickens with highly pathogenic avian influenza viruses in their BSL-3⁺ facility; Southern Drug Research for performing a human clinical trial of an adenovirus-vectored influenza (H1N1) vaccine; and Utah State University for validating the DVD data in their animal facilities.

Financial & competing interests disclosure

The authors at Vaxin Inc. and Auburn University are shareholders of Vaxin Inc. and inventors on patents pertaining to adenovirus-vectored vaccines and/or DVD. They have also received grant support from the NIH (2R44AI068285-02, 1UC1AI067198-01 and 1UC1AI067205-1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.