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Immune Responses Shown in Covid-19 Nasal Vaccine

Nasal spray

(robin-24, Flickr, Wikimedia Commons)

14 July 2020. An experimental vaccine to prevent Covid-19 infections, given as a nasal spray, produces immune responses in tests with lab mice. Researchers at University of Alabama in Birmingham and the biotechnology company Altimmune Inc. in Gaithersburg, Maryland reported their findings yesterday.

Altimmune is a developer of drugs that invoke the immune system, including vaccines against infectious diseases. Among the company’s pipeline products is NasoVax, an influenza vaccine formulated as a nasal spray that Altimmune says in clinical trials generates protective antibodies as well as injected flu vaccines. In addition, says the company, NasoVax protects against infections in mucous membranes and generates T-cell responses in the immune system, with those immune responses lasting 12 to 14 months in about half of the participants.

Altimmune is also creating a nasal-spray treatment for Covid-19 infections, cleared last month by the Food and Drug Administration for clinical trials, and a nasal-spray vaccine to protect against inhaled anthrax infections, funded by BARDA, the U.S. government’s health emergency preparedness agency. Administering vaccines by nasal spray, says the company, reduces the need for trained health care workers, as well as refrigeration required for syringe-delivered vaccines.

In March, Altimmune and Alabama-Birmingham agreed to partner on preclinical tests of AdCovid, the company’s Covid-19 vaccine candidate. Alabama-Birmingham’s preclinical studies are led by microbiologist Frances Lund. Lund’s lab studies the role of B-cells in the immune system to produce antibodies, but also to generate cytokines, signaling molecules produced by the immune system implicated in allergies and autoimmune disorders.

AdCovid, says the company, is designed using a similar technology as NasoVax to produce multiple immune responses. The vaccine’s chemistry resembles receptor proteins in cells, where the SARS-CoV-2 virus’s spike protein binds, to begin the infection process. When binding to the spike protein, AdCovid aims to generate immunoglobulin G and A, or IgG and IgA, neutralizing antibodies in the blood and mucous membranes respectively, to prevent immediate Covid-19 infections, but also prevent infections from developing in the respiratory tract.

In the work for Altimmune, Lund and colleagues tested AdCovid in lab mice. One set of tests show AdCovid produces detectable levels of IgG antibodies in mice 14 days after a single dose. After 28 days, say the researchers, AdCovid generates a concentration of antibodies at twice the level than recommended by FDA for convalescent plasma, donated by individuals who recover from Covid-19 infections.

A second set of tests, says the study team, show a single dose of AdCovid produces IgA antibodies in mouse respiratory fluids in mucous membranes at levels 29 times higher than before vaccination, and well above IgA antibody levels produced in other vaccines designed to act in mucosal tissue. “The potent stimulation of mucosal IgA immunity in the respiratory tract,” says Lund in a statement, “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.”

Altimmune reports that other preclinical tests show AdCovid produces immune-system T-cells, dendritic, and natural killer cells in lab mice, also residing in the lymph nodes and spleen suggesting long-term protection against the SARS-CoV-2 virus. The company plans to release more details of these tests in the coming weeks, and expects to begin clinical trials of AdCovid by the fourth quarter of the year.

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