Altimmune Announces New Preclinical Data for AdCOVID Demonstrating Sterilizing Immunity After a Single Intranasal Dose

Altimmune, Inc. recently announced positive results from a preclinical study of AdCOVID in a SARS-CoV-2 challenge model of infection. In this study, a single intranasal dose of AdCOVID provided sterilizing immunity in the lungs of vaccinated mice, in contrast to the development of dense pulmonary infection and disease in the lungs of non-vaccinated mice following infection with SARS-CoV-2. AdCOVID is a novel, single-dose intranasal vaccine candidate for COVID-19.

“These latest data are very exciting, as they confirm and expand upon the numerous potential advantages of our differentiated intranasal vaccine approach,” said Scot Roberts, PhD, Chief Scientific Officer at Altimmune. “In the current study, we found a heavy burden of infectious SARS-CoV-2 virus in the lungs of non-vaccinated mice following challenge with the virus. Importantly, no detectable levels of infectious virus were observed in the lungs of AdCOVID-vaccinated animals. These data suggest that a single intranasal vaccination with AdCOVID may provide sterilizing immunity that neutralizes infectious virus, which is believed to be the best way to block viral transmission. Blocking transmission is critical for preventing spread of the virus and preventing the emergence of new variants of concern, both of which have the potential to prolong the pandemic. We continue to be encouraged by the accumulating preclinical data for AdCOVID and look forward to reporting the results of our ongoing Phase 1 clinical trial later this quarter.”

“Growing vaccine hesitancy, which is emerging as a real problem in the fight against SARS-CoV-2, underscores the importance of developing novel vaccine approaches like AdCOVID, which is a needle-free, thermostable vaccine that may be delivered in a single-dose and has the potential to prevent SARS-CoV-2 transmission. These attributes could foster vaccine acceptance, both nationally and globally. In addition, intranasally delivered AdCOVID could play a critical role in re-vaccination campaigns to control future spread of the virus, and ultimately to help bring an end to this devastating global pandemic,” added collaborator Frances Lund, PhD, Charles H. McCauley Professor and Chair for the Department of Microbiology at the University of Alabama at Birmingham (UAB).

In the current study, performed in collaboration with UAB, K18-hACE2 transgenic mice, which are highly permissive for SARS-CoV-2 replication and considered one of the best models for COVID-19, were vaccinated with a single intranasal dose of AdCOVID and challenged one month later with live SARS-CoV-2 virus.

When the lungs of the mice were evaluated for infectious SARS-CoV-2 virus, no detectable levels of infectious virus were observed in the lungs of vaccinated mice, representing a greater than one million-fold reduction of infectious virus compared to the non-vaccinated controls. This demonstration of sterilizing immunity is consistent with the stimulation of local and systemic immunity by AdCOVID shown in previous animal studies, including high serum neutralizing antibody and T cell responses, and most importantly, mucosal IgA responses in the respiratory tract.

In previously reported preclinical studies, AdCOVID was associated with a 29-fold induction of spike-specific IgA and resident memory T cell responses in the lungs of experimental animals, as well as robust systemic serum neutralizing antibody titers and T cell responses in the lung and spleen.

The ongoing AdCOVID Phase 1 clinical trial is evaluating the safety and immunogenicity of AdCOVID following a single dose or two intranasal doses administered one month apart and is expected to report topline data in June 2021. The trial is evaluating three different dose levels of AdCOVID and will measure local mucosal IgA responses in the nasaopharyngeal cavity, systemic serum immune responses, including serum neutralizing antibody relative to COVID-19 convalescent serum, and T cell responses directed against the spike protein receptor binding domain.

AdCOVID is a single-dose intranasal vaccine candidate for COVID-19. It is designed to stimulate a broad immune response including both systemic immunity (neutralizing antibody) and local immunity (mucosal IgA, resident memory T cells) in the nasal cavity and respiratory tract. In published preclinical studies (www.biorxiv.org/content/10.1101/2020.10.10.331348v1) conducted in collaboration with the University of Alabama at Birmingham, potent serum neutralizing antibody responses, T cell responses, and a robust induction in mucosal immunity were observed in mice following a single intranasal dose of AdCOVID. Mucosal immunity was characterized by IgA antibody and resident memory T cell responses in the respiratory tract, both of which are believed to be important in fighting infection, and importantly, transmission. In other preclinical studies, AdCOVID provided 100% protection against lethal SARS-CoV-2 challenge.

Based on data from Altimmune’s other intranasal platform vaccine candidates, AdCOVID is expected to have extended stability at room temperature that would allow for cold chain-free shipment of the vaccine. If demonstrated, AdCOVID could be stored in the common refrigerators found in community-based doctors’ offices and pharmacies for two years or more. The Company believes that these simple and convenient handling requirements, together with the potential ability to block SARS-CoV-2 transmission, could position AdCOVID as a leading intranasal COVID-19 vaccine.

Altimmune is a clinical stage biopharmaceutical company focused on developing intranasal vaccines, immune modulating therapies and treatments for liver disease. Our diverse pipeline includes proprietary intranasal vaccines for COVID-19 (AdCOVID), anthrax (NasoShield), and influenza (NasoVAX); an intranasal immune modulating therapeutic for COVID-19 (T-COVID); and next generation peptide therapeutics for NASH (ALT-801) and chronic hepatitis B (HepTcell). For more information, visit www.altimmune.com.