For effective management of the COVID-19 pandemic and its second wave, the design and implementation
of multiple intervention approaches are crucial. They include the development of effective antivirals, high-affinity
SARS-CoV-2-neuralizing human or humanized monoclonal antibodies, rapid diagnostic assays, immunogenic
and protective vaccines, strategies to mitigate virus transmissibility, and enhancing capacity related to trained
medical personnel, facilities, and supplies. Due to the possibility of antibody-dependent enhancement (ADE) of
COVID-19, vaccine efforts should consider the use of a novel vaccine platform and design of a relevant antigen
strategy. It is essential to note that the elderly are the most vulnerable segment of the population that is at a
higher risk of COVID-19 severity; the vaccine development efforts should, therefore, consider the decline in the
immune competence in the elderly.
We have developed a novel replication-defective (E1 & E3 deleted) bovine adenovirus (Ad) type 3 (BAd3)-
based vaccine platform, which is better than the currently available Ad vector systems for providing heterologous
influenza protection with dose sparing and is not impacted by the pre-existing human Ad vector immunity.
Recently, we have revealed that the BAd vaccine platform provides the expression of significantly higher levels
of the immunogen and innate and adaptive immunity-related factors compared to that of human Ad vectors in
mice. This work suggests that the BAd vector system could serve as an excellent delivery vehicle for the
development of recombinant vaccines against emerging pathogens for the elderly and other segments of the
population. We have also identified a 22 amino acid residues Autophagy-Inducing Peptide (AIP) C5 (AIP-C5)
from the CFP10 protein of M. tuberculosis that enhances robust T cell immune responses in mice to NP of H7N9
influenza virus when delivered through an Ad vector. It conferred complete protection against H1N1, H3N2,
H5N2, H7N9, and H9N2 influenza viruses.
The proposal is based on the hypothesis that immunization with the autophagy-inducing replication-deficient
BAd vector expressing relevant antigen/s of SARS-CoV-2 will strengthen an effective mucosal (lung) and
systemic anti-COVID-19 immunity. Under Aim 1, we will evaluate the immunogenicity and protective
efficacy of a novel vaccine platform and antigen design in animal models for developing an effective
COVID-19 vaccine. Whereas under Aim 2, we will investigate the vaccine-induced antibody-dependent
enhancement (ADE) of SARS-CoV-2 infection, the quality of memory innate, B and T cell responses, and
the durability of protective immunity in the best animal model. We believe that the use of a unique
nonhuman Ad vaccine platform and novel antigen design containing AIP-C5 will yield an effective COVID-19
vaccine for all segments of the population. This effort will be of significant value to effectively flatten the COVID-
19 pandemic's trajectory and its second wave.