Editor’s note: Find the latest news and guidelines for COVID-19 at the Medscape Coronavirus Resource Center.
LISBON, Portugal – A total ninefold increase in antibody levels against COVID-19 can be seen with a longer interval between the first and second doses of Pfizer / BioNTech (BNT162b2) in people without a previous infection, according to government SIREN data. of the United Kingdom (SARS-CoV-2 Immunity and Reinfection Assessment).
This interval-dependent level of antibodies varies with age, with those aged 45-54 showing an 11-fold increase over a longer dosing interval (more than 10 weeks vs. 2-4 weeks). People under the age of 25 show a 13-fold increase with the longer interval, but the number of participants is low in this subgroup.
Total antibody levels in participants who were not infected were 1268.72 antibody binding units (BAU) / mL (1043.25 – 1542.91) in those with a 2-4 week interval compared to 11,479 , 73 BAU / mL (10,742.76 – 7.40 <12). , in those with a dose interval of at least 10 weeks.
The work is the latest SIREN test, which measures the levels of antibodies in the blood of nearly 6,000 healthcare professionals across the UK. Study leader Ashley Otter, PhD, Technical Director of SIREN Serology at the UK Health Security Agency (UKHSA), will present her work on Tuesday at this year’s European Congress on Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon.
In an interview with Medscape Medical News, Otter noted that “it is important to remember that antibody levels are only one aspect of the immune response, and in our recent analysis of vaccine effectiveness, we found that dosing intervals did not affect protection against infection ”.
The study, which appeared in the March issue of the New England Journal of Medicine, also found that after the second dose of the vaccine, there was about a 2.5-fold difference in antibody levels between those who had a previous infection 16,052 (14,071-18,312) mL compared with 7,050 (6,634 – 7,491) BAU / mL in individuals not treated with infection (P <.0001).
Only after the first dose were antibody levels up to 10 times higher in participants who had previously been infected than in individuals who were not infected. This effect lasted up to 8 months and then began to occur.
Natural infection, elevated antibody levels
Otter noted that “COVID-19 antibody levels are high in those people who have previously been naturally infected and vaccinated, emphasizing that vaccination provides additional benefits for these people.”
Medscape asked Charlotte Thålin, PhD, an immunologist at the Karolinska Institute, Stockholm, Sweden, to comment on the study. Thålin is studying a cohort similar to SIREN, called the cohort of health workers in the Swedish community. “The new SIREN data underscore the importance of the number of antigen exposures and the time interval between them, whether vaccination exposure or infection exposure.
“We see similar data in our group of health workers in the Swedish COMMUNITY,” Thålin continued, “where pre-vaccination infection leads to more than a twofold increase in antibodies, neutralizing width and T-cell responses, and even greater increases over time. between infection and vaccination. “
However, she warned that they now see a high rate of breakthrough infections with the Omicron vaccine, and this is also true for people with a previous infection and three doses of the vaccine.
“As we approach a second booster – a fourth dose of vaccine – we must take into account that many people will have had up to five to six exposures of antigen in a short period of time, sometimes within a year,” she said. “This is an entirely new scenario, with many different combinations of vaccine and infection-induced immunity. We still don’t know the effects of these frequent immune exposures, and now we need to keep a close eye on immune responses after Omicron and booster doses.”
Initially, SIREN aimed to find out how much protection people received after developing a primary infection and why they could be re-infected with COVID-19. Following the introduction of the UK vaccination program, the protective effects of vaccination against COVID-19 have been studied, as well as why some people still become ill after vaccination, Otter explained.
In this latest analysis, Otter and colleagues evaluated spike-binding antibodies in serum samples from a total of 5,871 healthcare professionals, 3,989 after a single dose (at least 21 days) and 1,882 after two doses (at least 14 days).
The majority of participants are women (82.3%) and of white ethnicity (87%) and come from all over the United Kingdom.
Participants were also categorized into those who had evidence of natural infection with COVID-19 (confirmed by PCR test or suspected due to their antibody profile) or those who were not infected. Almost all (> 99%) of those who were not infected seroconverted after vaccination.
The primary outcome was anti-spike antibody levels as assessed by dose, previous infection, dosing interval, age, ethnicity, and comorbidities, including immunosuppressive diseases such as immune system cancer, rheumatic diseases, chronic respiratory disease, diabetes, obesity, and chronic neurological disease.
In the group that did not treat infection, the mean antibody (anti-S titer) was 75.48 BAU / mL after the first dose of vaccine, which rose to 7049.76 BAU / mL after the second dose.
The much higher titer of antibodies with the second dose in individuals who are not infected, “is what provides you with the greatest protection, because the titers of antibodies are at their peak. Then they begin to gradually decrease from this peak. said Otter.
In the post-infection group, antibody titers also increased (2111.08 BAU / mL after the first dose and 16 052.39 BAU / mL after the second dose), although less than in the naive group due to the additional exposure to infection, added Otter.
Antibody levels also vary depending on the time elapsed between natural infection and dose 1 of vaccination. With a 3-month interval, antibody levels were 1970.83 (1506.01 – 2579.1) BAU / mL compared to 13,759.31 (8,097.78 – 23,379.09) BAU / mL after a 9-month interval. . Single-dose antibody levels in those who were previously infected were higher than those who were not infected, as “previous infection, followed by vaccination, may be explained by T-cell expansion when amplified by a second exposure to antigen and then a maturing B-cell memory response has been proven for up to 6 months, ”Otter explained.
Time to take the fourth dose
By March of this year, 86.2% of the UK population over the age of 12 had received at least two doses, but with an increase in the prevalence of the disease and the prevalence of anxiety options,
Further work is underway to understand the weakening of the immune response, the level of protection and why some people develop COVID-19 even when they have been vaccinated twice.
Medscape asked Susanna Dunaci, BMChB, a professor of infectious diseases at Oxford University in the United Kingdom, what the results of the time intervals for the fourth dose of the vaccine might mean among the UK population.
In the United Kingdom, fourth doses are given to people aged 75 and over in old people’s homes and those with weakened immune systems. “To decide on fourth doses for healthy people, we need to see how quickly antibody and T cell responses decline,” said Dunaci, who is part of SIREN’s large research team but is not involved in the Otter-led analysis. “Current studies show that the T-cell response may be better maintained than the antibody response and less affected by variants such as Omicron.”
She explained the balance between antibody and T cell responses to vaccination. “Antibodies that neutralize the virus are likely to be important in preventing any infection, and they unfortunately decline over time, but T-cell responses are more resilient and help keep people from [the] hospital, “she said.
Dunaci added that it is necessary to wait and observe what happens next with the evolution of SARS-CoV-2, as well as to wait for a longer follow-up after the third dose in healthy people. “According to current evidence, my assessment is that we are postponing decisions on fourth doses in healthy people until the end of summer / autumn.”
32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID): Executive summary 250. To be presented on 26 April 2022.
For more news, follow Medscape on Facebook, Twitter, Instagram, YouTube and LinkedIn
Add Comment