The COVID-19 pandemic is over, but the virus that caused it is still here, sending thousands of people to the hospital every week and generating new variants with depressing regularity. The virus’s exceptional ability to shift and evade immune defenses has led the World Health Organization (WHO) to recommend annual updates to COVID-19 vaccines.
But some scientists worry that the remarkable success of the first COVID-19 vaccines could work against updated versions, undermining the usefulness of an annual vaccination program. A similar problem affects the annual flu vaccination campaign; Immunity from one year’s flu vaccines can interfere with immune responses in subsequent years, reducing the effectiveness of the vaccines.
A new study by researchers at Washington University School of Medicine in St. Louis helps address this question. Unlike immunity to the influenza virus, pre-immunity to SARS-CoV-2, the virus that causes COVID-19, does not inhibit post-vaccine responses. Rather, it promotes the development of broadly inhibitory antibodies, the researchers report.
The study, available online in Nature, shows that people who were repeatedly vaccinated against COVID-19 (initially receiving shots targeting the original variant, followed by boosters and updated vaccines targeting the variants) generated antibodies capable of neutralizing a broad range of vaccines. range of SARS. -CoV-2 variants and even some distantly related coronaviruses. The findings suggest that regular revaccination against COVID-19, far from hampering the body’s ability to recognize and respond to new variants, may cause people to gradually build up a reserve of broadly neutralizing antibodies that protect them from the emerging SARS-CoV. 2 and also some other coronavirus species, even those that have not yet emerged to infect humans.
“The first vaccine an individual receives induces a strong primary immune response that shapes responses to subsequent infection and vaccination, an effect known as imprinting,” said senior author Michael S. Diamond, MD, PhD, professor of medicine. Herbert S. Gasser. “In principle, the impression can be positive, negative or neutral. In this case, we see a strong impression that is positive, because it is coupled to the development of cross-reactive neutralizing antibodies with a remarkable breadth of activity.”
Impression is the natural result of how immunological memory works. A first vaccination triggers the development of immune cells with memory. When people receive a second vaccine quite similar to the first, the memory cells caused by the first vaccine are reactivated. These memory cells dominate and shape the immune response to the subsequent vaccine.
In the case of the flu vaccine, the impression has negative effects. Antibody-producing memory cells crowd out new antibody-producing cells, and people develop relatively few neutralizing antibodies against the newer vaccine strains. But in other cases, imprinting can be positive, promoting the development of cross-reactive antibodies that neutralize the strains in both the initial and subsequent vaccines.
To understand how imprinting influences the immune response to repeated COVID-19 vaccination, Diamond and his colleagues, including first author Chieh-Yu Liang, a graduate student, studied antibodies from mice or people who had received a sequence of COVID-19 vaccines and boosters targeting first the original variant and then the omicron. Some of the human participants had also been naturally infected with the virus that causes COVID-19.
The first question was the strength of the impression effect. The researchers measured how many of the participants’ neutralizing antibodies were specific to the original variant, the omicron variant, or both. They found that very few people had developed antibodies unique to omicron, a pattern indicative of strong imprinting after initial vaccination. But they also found few antibodies unique to the original variant. The vast majority of neutralizing antibodies cross-reacted with both.
The next question was to what extent the cross-reaction effect extended. Cross-reactive antibodies, by definition, recognize a characteristic shared by two or more variants. Some characteristics are shared only by similar variants, others by all SARS-CoV-2 variants or even by all coronaviruses. To assess the breadth of the neutralizing antibodies, the researchers tested them against a panel of coronaviruses, including SARS-CoV-2 viruses from two omicron lineages; a pangolin coronavirus; the SARS-1 virus that caused the 2002-03 SARS epidemic; and the Middle East respiratory syndrome (MERS) virus. The antibodies neutralized all viruses except the MERS virus, which comes from a different branch of the coronavirus family tree than the others.
Additional experiments revealed that this notable breadth was due to the combination of original and variant vaccines. People who received only the vaccines targeting the original SARS-CoV-2 variant developed some cross-reactive antibodies that neutralized the pangolin coronavirus and the SARS-1 virus, but the levels were low. However, after boosting with an omicron vaccine, cross-reactive neutralizing antibodies against the two coronavirus species increased.
Taken together, the findings suggest that regular revaccination with updated COVID-19 vaccines against variants could give people the tools to combat not only the SARS-CoV-2 variants represented in the vaccines, but also other SARS-CoV variants. -2. and related coronaviruses, possibly including some that have not yet emerged.
“At the beginning of the COVID-19 pandemic, the world’s population was immunologically naïve, which is part of the reason the virus was able to spread so quickly and cause so much damage,” said Diamond, also a professor of molecular microbiology and pathology and immunology. “We don’t know for sure whether receiving an updated COVID-19 vaccine each year would protect people against emerging coronaviruses, but it is plausible. These data suggest that if these cross-reactive antibodies do not decline rapidly, we would need to monitor their levels over the course of the year. time to know for sure: they may confer partial or even substantial protection against a pandemic caused by a related coronavirus.”