Summary Current COVID-19 vaccines significantly reduce overall morbidity and mortality and are critically important to control the pandemic. People who have previously recovered from COVID-19 have enhanced immune responses after vaccination (hybrid immunity) compared to their vaccinated peers without prior treatment; however, the effects of infections after vaccination on the humoral immune response remain to be determined. Here, we measured the neutralizing antibody responses of 104 vaccinated people, including those with advanced infections, hybrid immunity, and no history of infection. We found that human immune sera after advanced infection and vaccination after natural infection broadly neutralize SARS-CoV-2 variants to a similar degree. While age is negatively correlated with antibody response after vaccination alone, no correlation with age was found in the hybrid or breakthrough immune groups. Together, our data suggest that additional exposure to antigen from natural infection substantially increases the quantity, quality, and breadth of the humoral immune response, regardless of whether it occurs before or after vaccination. |
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A new study finds that two forms of immunity (sudden infections after vaccination or natural infection followed by vaccination) provide approximately equal levels of enhanced immune protection.
The new study published online today in the journal Science Immunology .
"It doesn’t matter if you get infected and then vaccinated, or if you get vaccinated and then advanced infection," said co-senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology at the OHSU School of Medicine. “In either case, you will get a very, very strong, incredibly high immune response.”
The research follows an OHSU study published in December that described extremely high levels of immune response after major infections, so-called "superimmunity . " That study was the first to use multiple live variants of SARS-CoV-2 to measure blood serum cross-neutralization of breakthrough cases.
The new study found that it doesn’t matter whether someone gets an advanced infection or gets vaccinated after a natural infection. In both cases, the immune response measured in blood serum revealed antibodies that were equally more abundant and more potent (at least 10 times more potent) than the immunity generated by vaccination alone.
The study was conducted before the emergence of the omicron variant , but researchers expect the hybrid immune responses to be similar to those of the new highly transmissible variant.
“The likelihood of getting advanced infections is high because there is so much virus around us right now,” Tafesse said. “But we position ourselves better by getting vaccinated. And if the virus arrives, we will have a milder case and we will end up with this super immunity.”
The researchers recruited a total of 104 people, all OHSU employees who were vaccinated with the Pfizer vaccine, and then carefully divided them into three groups: 42 who were vaccinated without infection, 31 who were vaccinated after an infection and 31 who had recurrent infections after vaccination.
Controlling for age, sex, and time since vaccination and infection, the researchers drew blood samples from each participant and exposed the samples to three variants of the live SARS-CoV-2 virus in a biosafety level 3 laboratory. on OHSU’s Marquam Hill campus.
They found that both groups with "hybrid immunity" generated higher levels of immunity compared to the group that was vaccinated without infection.
A path towards endemic COVID
With the wildly contagious omicron variant now circulating around the world, the new findings suggest that each new infection that advances potentially brings the end of the pandemic closer.
"At this point, I would expect many vaccinated people to end up with advanced infections and therefore a form of hybrid immunity," said co-senior author Bill Messer, M.D., Ph.D., assistant professor of molecular microbiology and immunology. and medicine (infectious diseases) at the OHSU School of Medicine
Over time, the virus will encounter a growing pool of human immunity.
OHSU scientists say they have not proven multiple rounds of natural infection, although many people likely fall into that category given that millions of people in the United States and around the world remain unvaccinated.
With the spread of the highly contagious omicron variant, many unvaccinated people who were previously infected are likely to face the virus again. For that group, previous research reveals a much more variable level of immune response than vaccination, Messer said.
“I can guarantee that immunity will be variable, and some people will get immunity equivalent to vaccination, but most will not,” he said. “And there is no way, short of laboratory testing, to know who gets what immunity. “Vaccination makes it much more likely to guarantee a good immune response.”
Co-senior author Marcel Curlin, MD, agreed. “Immunity from natural infection alone is variable. Some people produce a strong response and some don’t,” said Curlin, associate professor of medicine (infectious diseases) at the OHSU School of Medicine and director of OHSU Occupational Health. “But vaccination combined with immunity against infection almost always provides very strong responses.
"These results, together with our previous work, point to a time when SARS-CoV-2 may become a mostly mild endemic infection, such as a seasonal respiratory tract infection, rather than a global pandemic."
In addition to Tafesse, Messer, and Curlin, co-authors included Timothy Bates, Savannah McBride, Hans Leier, Gaelen Guzman, Zoe Lyski, Devin Schoen, Bradie Winders, Joon-Yong Lee of Pacific Northwest National Laboratory, and David Xthona Lee.
The study was funded by a grant from the MJ Murdock Charitable Trust; an unrestricted grant from the OHSU Foundation; the National Institutes of Health, training grant T32HL083808 and grant R01AI145835; and OHSU Innovative IDEA grant 1018784.
The study authors thank the research participants for their generous contributions; the OHSU COVID-19 Serology Study Team and the OHSU Department of Occupational Health for recruitment and specimen acquisition; and the OHSU clinical laboratory under the direction of Donna Hansel, M.D., Ph.D., and Xuan Qin, Ph.D., for SARS-CoV-2 testing and reporting.
