NEWPORT BEACH, Calif. — Some of the first rounds of COVID-19 vaccine clinical trials are headed toward the final phases. But a new round of a second-generation vaccine clinical trial has begun in Orange County. 

The first person in the country to get the new vaccine as a part of NantKwest Inc. and ImmunityBio's Phase 1 clinical trial for COVID-19 was Chen Cao. Cao looked straight forward as the syringe went in her left arm. She said it didn't hurt but says, "the second day there was some redness. Pretty bad."

But she said the rash-like redness went away after a day, so did the bruise where the needle went into her arm last week. The bruise is one of the symptoms Cao has been keeping track of in a symptom journal that looks like a spreadsheet. She is required to fill it out daily as a part of the clinical trial that is happening only at Hoag Memorial Hospital Presbyterian in Newport Beach.

During the trial, Cao will need to go to the hospital once a week for several weeks, then monthly for a total of a year. Hospitals and doctors visits aren't exactly at the top of Cao's favorite places to visit. Laughing, she said, "I'm not saying avoid. I'm just saying, Uhm, yeah, avoid!"

During this trial, Cao will be required to get two shots total, three weeks apart. As a kid, Cao did everything to avoid shots. 

"I would pretend to have a fever," she said. "I would pretend I had a cold. I just don't want a shot."

Despite her dislike of shots, Cao volunteer for the NantKwest/ImmunityBio vaccine trial because "I hate COVID," she said. 

The pandemic is why Cao said she didn't get the college graduation ceremony she had imagined this year as a graduate of the University of California, Irvine. Her family had planned to fly to the U.S. from Shanghai to be at her graduation ceremony. Cao also made plans to visit different places throughout the U.S. from San Francisco, to Las Vegas, to New York. 

"Our plan had to be canceled," Cao said. "So yeah. I just haven't seen my family for almost two years."

Cao was the first of what will be 35 volunteers taking part in this Phase 1 clinical trial. Dr. Philip Robinson, Hoag Hospital Newport Beach's medical director of infection prevention and principal investigator for COVID-19, said all participants will get a second-generation vaccine.

"The vaccine that we give you has only dead pieces of the COVID virus," Robinson said. "Therefore, there's no way you can get COVID from this vaccine."

He says first-generation vaccines currently in Phase 3 of clinical trials deliver the virus's dead pieces through another virus (adenovirus) that causes the common cold. And he added that since most of us have had a common cold, our immune systems are more likely to destroy the first generation vaccines. Dr. Robinson said the second generation vaccine uses a different delivery system. 

"It's stealth. It's invisible to our immune system," he said. "So it can deliver and help train the immune system before our immune system destroys it. " 

Robinson said he expects this vaccine to be more effective because it would give the body more time to build two types of fighters, including antibodies to prevent the virus from getting into cells. 

"Those cells destroy cells that have already been infected by SARS CoV 2," the doctor said, referring to T-cells.

He said this NantKwest/ImmunityBio vaccine is novel because it stimulates both arms of the immune system, including the cell-mediated immunity, in other words, the T-cell response. 

He said that's important because, "What we know, based on SARS-CoV 1, is that patients who developed that T-cell, cellular immune response have very long-lived immunity that can be measured 17 years after they got infected."

According to the company, T-cell responses are more robust than antibody responses triggered by the spike in protein alone and can form a much longer-term immunity. This vaccine's double-edged approach is a "key advantage" that could also overcome mutations in the spike proteins, which might limit the efficacy of "S-only" vaccines going forward.

Unlike other vaccines, Robinson said this particular vaccine won't need to be stored at super-cold temperatures, which can pose significant logistical challenges. Instead, it just needs standard refrigeration and can remain viable at room temperature, Robinson said. The vaccine might also be delivered by mouth or nasal spray down the line, rather than by injection.

Five volunteers got their first injections at Hoag last week, and five more will get their first injections this week. There will be a pause after each set of 10 to examine safety, side effects, and immune system responses.

The primary goal of this Phase 1 trial, according to Robinson, is to test the safety of the vaccine and see how the immune system responds. If all goes well, it will expand into Phases 2 and 3 next year, recruiting hundreds, and then thousands, of people.

For now, it will be about a year before we'll know whether this vaccine is effective during Phase 1. A long time for Cao to wait, but she said it's worth stepping up for because it allowed her to get back to giving back. 

Cao had regularly volunteered for different organizations, including tutoring kids and helping out at an animal shelter, but she said pandemic put a pause on those opportunities. She said not being able to give back has been weighing on her. 

"For so long, I haven't been able to do any good things," she said.