The first two COVID-19 vaccines authorized by the Food and Drug Administration (FDA) utilized mRNA technology previously unused in FDA-approved vaccines. One of its chief proponents bounced from research job to research job for low pay because government-controlled science funding prefers guaranteed success for each round of funding rather than the hit-but-we'll-mostly-miss basic research approach of the private sector. mRNA-based vaccines provide instructions for the body to build and release foreign proteins, such as the spike protein in the case of the SARS-CoV-2 virus, but prior to the pandemic government funding agencies believed mRNA was a waste of time.
Now everyone will be rushing to advance mRNA but what is yet to be known; will the benefits last?
A study in Nature finds that people who received the Pfizer vaccine still had germinal centers - formed as the result of natural infection or vaccination which are basically boot camps for immune cells to improve - in their lymph nodes churning out immune cells directed against SARS-CoV-2 nearly four months later.
A better germinal center response may equal a better vaccine and vaccination led to high levels of neutralizing antibodies effective against three variants of the virus, including the Beta variant from South Africa that has shown some resistance to vaccines. Vaccination induced stronger antibody responses in people who had recovered from SARS-CoV-2 infection compared to those who had never been infected.
In April, both Pfizer and Moderna reported that their vaccines provided at least six months of protection. Their reports were based on tracking whether vaccinated people came down with COVID-19. Other groups have monitored antibody levels in the blood and concluded that the vaccine provides at least months of protection. But nobody had looked to see how the immune response was developing in the body, which could provide important clues to the strength and persistence of the immune response without requiring years of follow-up.
Scientists don’t yet understand why some vaccines, such as the one for smallpox, induce strong protection that lasts a lifetime, while others, such as the vaccine for whooping cough, require regular boosters. But many suspect that the difference lies in the quality of the germinal centers induced by different vaccines.
To get answers, the team performed ultrasound-guided sampling of the minuscule germinal centers in lymph nodes in the armpit. They extracted cells from 14 people who received the Pfizer vaccine. Samples were obtained three weeks after the first dose (just prior to administration of the second dose), and at weeks four, five and seven. Ten of the participants gave additional samples 15 weeks after the first dose. None of the participants previously had been infected with the virus that causes COVID-19.
Three weeks after the first dose, all 14 participants had formed germinal centers with B cells producing antibodies that target a key SARS-CoV-2 protein. The response expanded greatly after the booster shot and then stayed high. Even 15 weeks after the first dose, eight of 10 people still had detectable germinal centers containing B cells targeting the virus.
The researchers also obtained blood samples from 41 people who received the Pfizer vaccine, including eight who previously had been infected with the virus that causes COVID-19. Samples were obtained prior to the administration of each dose of the vaccine, as well as at weeks four, five, seven and 15 after the first dose. In people without prior exposure to the virus, antibody levels rose slowly after the first dose and peaked one week after the second. People who previously had been infected already had antibodies in their blood before the first dose. Their levels shot up quickly after the first dose and peaked higher than the uninfected participants’ levels.
“We didn’t set out to compare the effectiveness of vaccination in people with and without a history of infection, but when we looked at the data we could see an effect,” said co-first author Jane O’Halloran, MD, PhD, assistant professor of medicine at Washington University School of Medicine in St. Louis. “If you’ve already been infected and then you get vaccinated, you get a boost to your antibody levels. The vaccine clearly adds benefit, even in the context of prior infection, which is why we recommend that people who have had COVID-19 get the vaccine.”