Superimmunity against COVID: how is it generated, according to Harvard experts

More and more scientific evidence postulates that vaccination plus natural immunity from exposure to coronavirus leads to particularly strong protection, even against many variants of the virus. The so-called hybrid immunity, that is, the natural immunity of an infection combined with the immunity provided by the vaccine, seems to result in stronger protection than simple infection or separate vaccination.

Thus, the vaccine against COVID-19 plus infection can lead to months of immunity, according to Harvard scientists in new studies carried out to find out what protection this acquired dual immunity confers.

Miguel Hernan, an epidemiologist at Harvard's T.H. Chan School of Public Health in Boston, Massachusetts, said that studies show the near-universal benefit of full vaccination, even in those who have already suffered COVID-19. And he warned that some nations have issued statements encouraging people who have had COVID-19 to receive a single dose of vaccine: a measure that “may be justified in an environment of shortage of vaccines, but that is not appropriate when it comes to being properly protected at the immune level,” said the expert.

Not long after countries began implementing vaccines, researchers began to notice unique properties of vaccine responses from people who had previously been infected and recovered from COVID-19.

“We saw that antibodies reach these astronomical levels that exceed what is obtained with two doses of vaccine alone,” explained Rishi Goel, an immunologist at the University of Pennsylvania in Philadelphia, who is part of a team that studies superimmunity, or hybrid immunity, as most people call it scientists.

In a recent scientific study carried out in Brazil and published in The Lancet, he collected data from patients infected and vaccinated before the emergence of the Ómicron variant. Julio Croda, infectiologist and epidemiologist at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Croda and his colleagues analyzed Brazil's vaccination and infection databases to prove that the claims of Brazilian President Jair Bolsonaro, who said that since he already had COVID-19, so it was not necessary to get vaccinated, were wrong.

Researchers found that between February 2020 and November 2021, people who had previously been infected with SARS-CoV-2 and then received a dose of the vaccine — manufactured by Pfizer-BioNTech, Oxford-AstraZeneca, SINovac, or Johnson & Johnson — avoided up to 45% of COVID-19 cases that the group would have been expected to contract without vaccination.

Full courses of two-dose vaccines prevented up to 65% of expected infections and more than 80% of expected cases of severe COVID-19. “The big message is this: it is necessary to have a complete vaccination schedule for COVID-19,” Croda said.

Some authorities consider previous infections when deciding who should have access to public places, such as concerts and restaurants, but others consider only vaccination status. Peter Nordström, an epidemiologist at the University of Umeå, in Sweden, says that this dichotomy led him and his colleagues to do another study.

Using records collected by the Swedish Public Health Agency between March 2020 and October 2021, the researchers showed that Swedish residents who had been infected with SARS-CoV-2 had a 95% reduction in the risk of contracting COVID-19 compared to people who had not had immunity, and protection grew during the three months after infection and lasted until at least 20 months after infection. One dose of the vaccine reduced the risk of infection by about 50% more, and a second dose stabilized additional protection for six months after vaccination.

Although vaccination increases protection, Nordström believes that the immunity offered by infection alone is worthy of consideration. “Maybe we should have immunity passports instead of vaccination passports. Therefore, it is considered immune, and it is less likely to transmit the disease, if you have been fully vaccinated or if you have had a previous documented infection,” he said.

Epidemiologist Victoria Hall of the UK Health Safety Agency in London and her colleagues conducted the third study by monitoring infections in thousands of healthcare workers from March 2020 to September 2021. Researchers found that previous infections prevented more than 80% of COVID-19 cases that would otherwise have been expected in the year after infection, but protection dropped to around 70% after a year.

Study participants who received two doses of the Pfizer-BioNTech or Oxford-AstraZeneca vaccine after infection had close to 100% protection for at least six to eight months after the second dose. “Protection declined over time after vaccination and also after infection, but remained persistently high in those with hybrid immunity,” Hall concluded of recent research.

More research on hybrid immunity

Initial studies of people with hybrid immunity found that their serum, the portion of blood that contains antibodies, was much better able to neutralize immune-evading strains, such as the Beta variant identified in South Africa, and other coronaviruses, in compared to vaccinated people who had never faced SARS-CoV-2. It was not clear whether this was due only to high levels of neutralizing antibodies or other properties.

The most recent studies suggest that hybrid immunity is due, at least in part, to immune agents called memory B cells. Most of the antibodies produced after infection or vaccination come from short-lived cells called plasmablasts, and antibody levels drop when these cells inevitably die. Once plasmablasts disappear, the main source of antibodies becomes much rarer memory B cells that are triggered by infection or vaccination.

A separate study found that, compared to mRNA vaccination, infection leads to a group of antibodies that recognize variants more uniformly by targeting various peak regions. The researchers also found that people with hybrid immunity produced consistently higher levels of antibodies, compared to vaccinated people who were never infected, for up to seven months. Antibody levels were also more stable in people with hybrid immunity, reports the team led by immunologist Duane Wesemann at Harvard Medical School in Boston, Massachusetts.

Many hybrid immunity studies have not followed vaccine recipients who had not been previously infected for as long as those who recovered from COVID-19, and their B cells may produce antibodies that gain potency and amplitude over time, additional doses of vaccine, or both. It can take months for a stable group of memory B cells to establish and mature.

“It's not surprising that people who are infected and vaccinated are getting a good response,” said Ali Ellebedy, B-cell immunologist at the University of Washington in St. Louis, Missouri. “We're comparing someone who started the race three or four months ago to someone who started the race now.”

There is some evidence that people who received both jabs without being previously infected appear to be catching up. Ellebedy's team collected lymph node samples from individuals vaccinated with mRNA and found signs that some of their vaccine-triggered memory B cells were acquiring mutations, up to 12 weeks after the second dose, which allowed them to recognize various coronaviruses, including some that cause common colds.

KEEP READING: