The investigational vaccine, Ad4-H5-VTN, is a recombinant, replicating adenovirus vaccine designed to spur antibodies to hemagglutinin, a protein found on the surface of influenza viruses. It has been developed by Gaithersburg, Maryland company Emergent Biosolutions.
The vaccine platform could be adapted against other viruses including SARS-CoV-2 and HIV.
Advantages over existing vaccines
Immunization with replication-competent recombinant vectors may drive more potent and durable immunity compared to non-replicating vaccines, because they can express viral proteins at higher levels and for longer durations, note the authors of the study.
Additionally, this type of vaccine induces a mucosal immune response that helps limit transmission of viruses that infect mucosal tissues.
The Phase 1 trial administered the vaccine intranasally to 28 study participants, as well as an oral capsule to 10 participants and via a tonsillar swab to 25 participants. The trial covered healthy men and non-pregnant women aged 18-49.
The participants who received the vaccine intranasally or via tonsillar swab showed significantly higher H5-specific neutralizing antibody levels compared to the group receiving the vaccine capsule orally.
The participants who received the intranasal vaccine shed viral DNA for two-to-four weeks, but virus could be cultured for a median of only one day. Participants had evidence of H5-specific CD4+ and CD8+ T-cell responses.
Volunteers who received the intranasal vaccine had high levels of serum neutralizing antibodies at 26 weeks after vaccination, and this level was unchanged at three to five years after a single intranasal dose of the vaccine. The duration of viral shedding correlated with a high magnitude of neutralizing antibody response at week 26. In addition, the intranasal vaccine induced a mucosal antibody response in the nose, mouth and rectum.
Source: K Matsuda et al. A Replication Competent Adenovirus-Vectored Influenza Vaccine Induces Durable Systemic and Mucosal Immunity. Journal of Clinical Investigation DOI: doi.org/10.1172/JCI140794.