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LISBON, Portugal – An overall nine-fold increase in COVID-19 antibody levels can be seen with a longer interval between the first and second doses of the Pfizer/BioNTech (BNT162b2) vaccine, according to data from the UK government’s SIREN. (SARS-CoV-2 Immunity and Reinfection Evaluation) Study.
This interval-dependent antibody level varied by age, with people aged 45–54 years showing an 11-fold increase with a longer dosing interval (over 10 weeks versus 2–4 weeks). Those under the age of 25 showed a 13-fold increase with longer intervals, but the number of participants in this sub-group was smaller.
Total antibody levels in infection-naive participants were 1268.72 binding antibody units (BAU)/mL (1043.25 – 1542.91), compared with 11,479.73 BAU/mL (10,742.78 – 12,267.24) over a 2–4 week interval.P <.0001), in people with a gap of at least 10 weeks between doses.
The work is the latest analysis from SIREN, which measured antibody levels in the blood of around 6000 healthcare workers across the UK. Study lead Ashley Otter, PhD, technical lead for siren serology at the UK Health Security Agency (UKHSA), will present the work on Tuesday at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon.
in an interview with Medscape Medical NewsOtter said that, “It is important to remember that antibody levels are only one aspect of the immune response and in our recent vaccine effectiveness analysis we found that the dose interval does not affect protection against infection.”
The study, which appeared in the March issue New England Journal of MedicineIt was also found that after the second dose of vaccine, there was an approximately 2.5-fold difference in antibody levels between those with 16.052 (14.071–18.312) BAU/mL compared to 7.050 (6.634 – 7.491) BAU/mL in infection. – naive person (P <.0001).
After only the first dose, antibody levels were 10-fold higher in participants who had previously been infected than in infection-naive individuals. This effect lasted for 8 months and then started to plateau.
increased levels of natural infection antibodies
Otter commented, “There are higher levels of COVID-19 antibodies in people who have previously been naturally infected and vaccinated, highlighting that vaccination provides an additional benefit to these individuals.”
Medscape asked Charlotte Thalin, PhD, an immunologist at the Karolinska Institutet, Stockholm, Sweden, to comment on the study. Thlin studies a group similar to SIREN, called the Swedish Community Health Activist Group. “The new data from Siren emphasizes the importance of the number of antigenic exposures and the time interval between them, whether it is exposure through vaccination or exposure through infection.”
“We see similar data in our Swedish community healthcare worker cohort,” Thalin continued, “where there is a more than two-fold increase in pre-vaccination infection antibodies, width of neutralizing, and T-cell responses, and a longer produces an even larger increase with the interval between infection and vaccination.”
However, he cautioned that they now see a higher rate of Omicron vaccine breakthrough infections, and the same is true in people with previous infections and three vaccine doses.
“As we approach a second booster – a fourth vaccine dose – we need to consider that many individuals will have five to six antigen exposures within a short period of time, sometimes a year,” she explained. . “This is a completely new scenario, with different combinations of vaccine and infection-induced immunity. We do not yet know the impact of these persistent immune exposures, and we now need to closely monitor immune responses following omicron and booster doses.” is required. “
The original objective of SIREN was to understand how much protection people had after developing a primary infection and why they could be reinfected with COVID-19. Following the rollout of the UK’s vaccination programme, the protective effects of vaccination against COVID-19 were examined as well as why some people still become ill after vaccination, Otter explained.
In this latest analysis, Otter and colleagues assessed anti-spike binding antibodies in serum samples from a total of 5871 healthcare workers, including 3989 after a single dose (at least 21 days) and 1882 after two doses (at least 14 days). days).
The majority of participants were female (82.3%) and of white ethnicity (87%) and came from across the UK.
Participants were also classified into those who had evidence of natural COVID-19 infection (confirmed by a PCR test or assumed because of their antibody profile) or those who were infection-naive. Almost all of them (>99%) who were infection-naive seroconverted after vaccination.
Primary outcome Anti-spike antibody levels were assessed according to dose, previous infection, dosing interval, age, ethnicity, and comorbidities, including immune-related diseases such as cancer of the immune system, rheumatoid disease, chronic respiratory disease, diabetes, obesity, and chronic disease is involved. Neurological diseases.
In the infection-nave group, the mean antibody (anti-S titer) was 75.48 BAU/mL after the first vaccine dose, and increased to 7049.76 BAU/mL after the second dose.
Very high antibody titers with the second dose in infection-naive individuals, Otter said, “is the one that gives you the most protection, because your antibody titers are at their peak. Then they start to drop slowly from this peak.” Huh.”
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 compared to the infection-naive group due to the additional risk of infection Less, Otter added.
Antibody levels also vary according to the time elapsed between natural infection and the vaccination dose. With a 3-month interval, the antibody level was 1970.83 (1506.01 – 2579.1) BAU/mL, while after a 9-month interval it was 13,759.31 (8,097.78 – 23,379.09) BAU/mL. Antibody levels after a single dose in previously infected people are higher than infection-naive because “previous infection, then vaccination, possibly explained by T-cell expansion upon promotion with a second antigen exposure, and then a mature memory B-cell response that has been demonstrated for up to 6 months,” Otter explained.
timing of fourth dose
As of March of this year, 86.2% of the UK population over the age of 12 had received at least two doses, but with the increase in the prevalence of the disease and the prevalence of forms of anxiety,
Further work is underway to understand the level of protection, decreased immune response, and why some individuals develop COVID-19 even after being double-vaccinated.
Medscape asked Susanna Dunacchi, BMCHB, Professor of Infectious Diseases, University of Oxford, UK, what the findings might mean for the timing of the fourth dose of the vaccine in the UK population.
In the UK, the fourth dose is being given to people 75 years of age and older, people living in care homes for older people and those with weakened immune systems. “To make a decision about a fourth dose for healthy people, we need to look at how quickly the antibody and T-cell responses drop,” said Dunacchi, who is part of the larger Sirens study team but also of Otter. Leadership was not involved in the analysis. “Current research suggests that the T-cell response may be better maintained than the antibody response, and is less affected by forms such as Omicron.”
He explained the balance between antibody and T-cell responses to vaccination. “It is likely that neutralizing antibodies to the virus are key to preventing any infection, and unfortunately these drop over time, but T-cell responses are better and help keep people out of it. [the] hospital,” she said.
Dunacchi said it’s important to wait and see what happens next with the development of SARS-CoV-2, as well as longer follow-up waiting times after the third dose in healthy people. “On the current evidence, my guess is that we postpone a decision on a fourth dose in healthy people until late summer/autumn.”
32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID): Abstract 250. To be submitted on April 26, 2022.
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