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Which is better for developing immunity: COVID-19 vaccine or natural infection?

Debate has raged over which provides better protection against COVID-19 — natural infection or vaccine injection?

“Sorry Dr Fauci and other fearmongers, new study shows vaccines and naturally acquired immunity DO effectively neutralize COVID variants. Good news for everyone but bureaucrats and petty tyrants!” tweeted a combative Kentucky Sen. Rand Paul in March.

A large-scale study by UC Irvine researchers may definitively settle this debate. They found that, yes, natural infection provides protection, but mRNA vaccines like Pfizer and Moderna kick natural immunity’s butt in protecting against COVID-19.

“Our results show that the nucleic acid vaccines in use in this setting are remarkably effective at elevating (antibody) levels against SARS-CoV-2 antigens,” says the study, posted April 20. The level and breadth of protection induced by these mRNA vaccines “is much greater than that induced by natural infection.”

A nurse prepares Pfizer-BioNTech COIVD-19 vaccines in Riverside on April 15. (Photo by Terry Pierson, The Press-Enterprise/SCNG)

Indeed, after the second mRNA shot, vaccinated people had antibody levels up to 10 times higher than what was found in convalescent plasma from people who recovered from natural infection, the researchers found.

Added bonus: The mRNA vaccines also allow the immune system to recognize other novel coronavirus strains, offering hope that vaccination will be effective against emerging virus variants that are circulating around the world, they said.

“This is a pretty spectacular thing,” said Philip L. Felgner, director of UC Irvine’s Vaccine Research and Development Center and Protein Microarray Laboratory and Training Facility, who was one of the researchers. “It’s not just doing something for a relatively small group of patients with uncommon disease — here we’re talking about saving the whole world.”

Hide and seek

The mRNA vaccines eclipsed natural infection at one very specific task: recognizing the precise piece of the virus’ spike protein that binds to — and infects — healthy cells.

The spike protein is big, Felgner said. And in natural infections, the virus manages to hide this vital receptor so the immune system doesn’t see it. And if the immune system doesn’t see it, it can’t develop antibodies to it.

“When a person gets infected they develop an immune response, but it’s not against this most important part,” Felgner said. “So the virus can evade the immune response that we develop, and that’s really favorable for the virus. It means it can go on out and propagate in the world, mutate itself more, make more variants.”

But that doesn’t happen with mRNA vaccines. The mRNA instructs the body to manufacture the piece of the spike protein with this otherwise-hidden receptor — which allows the body to produce antibodies to it.

Since vaccination induces a more robust immune response than natural exposure alone, those who’ve recovered from COVID may  benefit from getting vaccinated, the paper found.

Scientific excitement

Outside experts were buoyed by the findings.

“I was hoping for this, and it was reflected in developmental animal data. But to actually see it work is amazing,” said Dr. Brigham C. Willis, senior associate dean for medical education at the UC Riverside School of Medicine, who also was not involved.

“This represents a huge step forward in our ability to combat emerging and existing diseases. This new technology is so powerful. Now we can produce vaccines against a huge variety of disease that were heretofore impossible, and incredibly fast. The fact that it produces immunity much higher and more broadly against these difficult and mutating pathogens is huge. It will be very simple to produce boosters that include variants.

“It should also be exciting in the next couple of years, as I imagine we will now be able to produce effective vaccines against a variety of things we could not before — the common cold, perhaps flu, maybe even other things,” Willis said.

George Rutherford, a professor of epidemiology and biostatistics at UC San Francisco who also was not involved in the research, said, “Vaccine-induced immunity provides much, much higher levels of neutralizing antibody, at least in the medium term.”

Next steps

The study must be peer-reviewed, Felgner said, and clinicians and public health officials should use the data to inform patients and public health policy.

Researchers are measuring how long vaccine-induced immunity lasts — to guide the timing of future booster shots — and they’ll compare the immune responses induced by different types of vaccines, such as mRNA (Moderna, Pfizer) and adenovirus delivery systems (Johnson & Johnson, AstraZeneca).

In one area of concern, the UCI researchers found that immune-compromised people — such as those who’ve had organ transplants and are on immune-suppressing drugs — don’t develop high antibody levels after vaccination. “We need to discover ways to boost immunity in the immune compromised,” Felgner said.

The big takeaway is that mRNA vaccine-induced antibody levels are spectacular and appear rapidly within a few days after vaccination, he said. “Only in our dreams we could have imagined a vaccine that could be developed so quickly, works so well, can be manufactured at scale, distributed and administered to billions of people worldwide within months.”

But this isn’t a scientific miracle, he said. Nucleic acid vaccination was discovered 30 years ago and has been the passion of hundreds of scientists over the decades, backed by billions of dollars of investment, including millions from the National Institutes of Health.

“It shows how we make progress in science,” Felgner said. “Sometimes people complain, ‘Why are we giving all this money to the NIH?’ A reason is, so we can be prepared like we are today to respond to this outbreak.”

The researchers used data from several different studies in Orange County of thousands of people. To detect antibody levels, they used a coronavirus antigen microarray that is the intellectual property of the Regents of the University of California and licensed for commercialization to Nanommune Inc., a private company in which Felgner and several co-authors own shares.

Source: Orange County Register

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