Intranasal COVID-19 Vaccine Candidate Demonstrates Positive Results in Preclinical Studies

Preclinical studies of an intranasal COVID-19 vaccine candidate have showed strong serum neutralizing activity and potent mucosal immunity in the respiratory tract.

Altimmune, Inc. (Gaithersburg, MD, USA) conducted studies of its intranasal COVID-19 vaccine candidate, AdCOVID in collaboration with the University of Alabama at Birmingham (UAB Birmingham, AL, USA). The induction of IgA antibody in the respiratory tract may be necessary to block both infection and transmission of the virus to prevent further spread of COVID-19. Based on these findings, Altimmune plans to begin manufacturing of AdCOVID and advance the vaccine candidate to a Phase 1 safety and immunogenicity study in Q4 of this year.

AdCOVID is designed to express the receptor binding domain (RBD) of the SARS-CoV-2 virus spike protein, a key immune target that is essential for the virus to bind to cells and initiate infection. By focusing the immune response to this portion of the viral spike protein, AdCOVID elicited a strong systemic antibody response against RBD in mice, achieving serum IgG antibody concentrations greater than 800 micrograms per milliliter just 14 days after administration of a single intranasal dose. In addition, AdCOVID stimulated serum viral neutralization titers of 1:320 by Day 28, and two times higher than the titer recommended by the US FDA for investigational convalescent plasma as a treatment for severe COVID-19. In a separate study conducted by UAB, a single intranasal dose of AdCOVID stimulated a 29-fold induction of mucosal IgA in bronchoalveolar fluid of vaccinated mice. This level of IgA antibody stimulation is well above that associated with protection from disease in clinical studies of other mucosal vaccines.

In preclinical studies, vaccination with AdCOVID caused the rapid recruitment of immune cells into the respiratory tract and draining lymph nodes consistent with induction of mucosal and systemic immunity. Increases in CD8+ and CD4+ T cells, dendritic cells and NK cells were observed in the respiratory tract, and germinal center and memory B cells as well as T follicular helper cells were observed in regional lymph nodes and the spleen. Importantly, the latter cell types have been associated in prior vaccine development research with long-lived antibody responses. Preclinical data for antigen-specific T cell response are expected in the coming weeks. Intranasal dosing provides AdCOVID with the potential to be administered rapidly and without the need for needles, syringes or trained healthcare personnel. In addition, AdCOVID’s expected room temperature stability profile may allow for broad distribution of the vaccine without the need for expensive cold-chain logistics, such as refrigeration or freezing.

“Stimulation of immunity at this level just 14 days after a single dose is impressive for any vaccine, and is particularly notable for a potential coronavirus vaccine”, said Dr. Frances Lund, Charles H. McCauley Professor and Chair, Department of Microbiology at UAB, and lead investigator for preclinical testing of the AdCOVID vaccine candidates. “The potent stimulation of mucosal IgA immunity in the respiratory tract may be crucial to effectively block infection and transmission of the SARS-CoV-2 virus given that the nasal cavity is a key point of entry and replication for the SARS-CoV-2 virus.”

Related Links:
Altimmune, Inc.
University of Alabama at Birmingham