First in Human: Nasal vaccine for COVID-19, flu; diagnosing Alzheimer's early

This is a recurring column on clinical research in the early stages of development, which is referred to as phase 1. These are treatments being used for the first time in a small number of human patients to determine safety, dosing and general pharmacological activity.

A new nasal vaccine in development could not only offer a solution for anyone with a fear of needles, but also be harnessed against COVID-19 or flu.

The DelNS1 vaccine, being developed by the University of Hong Kong and the Coalition for Epidemic Preparedness Innovations, or CEPI, was the first nasal spray immunizer for COVID-19 to be tested on humans. However, the University of Hong Kong said it started researching nasal vaccines about three to four years ago for seasonal influenza, aiming to prevent people from catching flu by delivering a weakened version of the virus to spark an immune response and generate antibodies.

"Immunization via muscle injection will induce systematic immune response but it is not clear how much immunity will reach the respiratory tract, especially the upper respiratory tract. The nasal spray vaccine is designated more especially to induce immunity in the airway," Chen Honglin, professor of microbiology at the University of Hong Kong, told S&P Global Market Intelligence.

Unlike AstraZeneca PLC's FluMist, the only approved nasal vaccine for flu, creating DelNS1 involves removing the NS1 gene segment of the virus, which otherwise supports replication. Without this segment, the weakened live virus in the vaccine can only multiply for one round inside the cells of the upper airway. Researchers can also replace the empty space with the spike protein from the surface of the SARS-CoV-2 virus or another virus.

Early-stage data is already being assessed from a phase I/II trial by Beijing Wantai Biological Pharmacy Enterprise Co. Ltd. — supported by $4.89 million in funding from CEPI and a grant from Hong Kong's Health and Medical Research Fund — that launched in mainland China in September. The University of Hong Kong said it will kick off its own phase 1 study of the nasal vaccine in April.

"Animal experiments also show it can induce [similar] systematic immunity as other vaccines. It can be used in combination with other vaccines to boost immunity in the airway if the original immunity diminishes after a period of time of vaccination," Chen said.

The professor said the team plans to further enhance the vaccine and expand the application.

"We are continuing to improve this nasal spray vaccine platform for more immunogenicity and make it easier to manufacture. We are also making vaccines to target emerging variants [and] exploring the application of this platform for other chronic diseases, including cancers. While it can be used for nasal spray, it can also be used via injection," Chen said.

Other labs and companies around the world are looking into nasal vaccines amid the pandemic. U.S. biotech Codagenix Inc., for example, started a phase 1 trial for its own nasal COVID-19 vaccine in January.

"Same as mRNA vaccines, there are more investors during the pandemic. Nasal delivery of vaccines is being actively explored right now for the response in the next stage of the pandemic," said Chen.

Eyes offer window into Alzheimer's

Early diagnosis has long been a goal in the struggle against Alzheimer's, a neurodegenerative disease that still does not have an effective cure.

However, research by the Johns Hopkins Wilmer Eye Institute suggests the blood flow in the back of the eyes could one day help doctors detect the condition early without invasive procedures.

In the study, researchers assessed images of blood flow in the back of the eyes of 13 patients with a rare, genetically inherited form of early-onset Alzheimer's disease categorized by mutations in three genes. The images were acquired using optical coherence tomography angiography, a type of imaging technology that can visualize blood vessels down to the capillary level.

The blood vessel images showed that patients with the mutations — which affect about 1% of all individuals with the disease — have abnormally high and heterogeneous blood flow in their retinal capillaries, even when they had no signs of Alzheimer's.

This could help doctors diagnose earlier and start treatment to slow down patients' cognitive decline. However, researchers said further study is needed to see how reliable the method is.

"This type of non-invasive and rapid method of assessing capillary level blood flow may be very useful as a screening tool in the future. We would need larger and prospective studies to determine the accuracy of the method in this rare form of the disease as well as for other patients," Amir Kashani, associate professor of ophthalmology at Johns Hopkins University School of Medicine, told S&P Global Market Intelligence.