More antibodies with longer intervals between doses of the COVID vaccine

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LISBON, Portugal – An overall nine-fold increase in COVID-19 antibody levels with a longer interval between the first and second doses of the Pfizer/BioNTech (BNT162b2) vaccine could be seen in people with no previous infection, according to data from the UK government’s SIREN ( SARS-CoV-2 assessment of immunity and re-infection).

This interval-dependent antibody level varied by age, with those aged 45-54 years showing an 11-fold increase with a longer dosing period (greater than 10 weeks vs. 2-4 weeks). Subjects <25 years of age showed a 13-fold increase with the longer interval, but the numbers of participants were low in this subgroup.

Total antibody levels in the uninfected participants were 1268.72 BAU/mL (1043.25 – 1542.91) in those with a 2-4 week interval compared to 11,479.73 BAU/mL (10.742.78 – 1227.24) (s <.0001), in those with an interval of at least 10 weeks between doses.

The work is the latest analysis from SIREN, which measured the antibody levels in the blood of nearly 6,000 healthcare workers from across the UK. Ashley Otter, study leader, PhD, and technical lead for SIREN serology at the UK Health Security Agency (UKHSA), will present the work on Tuesday at this year’s European Conference on Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon.

In an interview with Medscape Medical NewsOtter noted, “It is important to remember that antibody levels are only one aspect of the immune response and in our recent analysis of vaccine efficacy we found that dosing intervals did not affect protection against infection.”

The study, which appeared in the March issue of C New England Journal of Medicinealso found that after the second dose of vaccine, there was a 2.5-fold difference in antibody levels among those previously infected with 16,052 (14.071-18.312) BAU/mL compared to 7.050 (6.634 – 7.491) BAU/mL in infected individuals. juniors (s <.0001).

After only the first dose, antibody levels were up to 10 times higher in the previously infected participants than in the infection-naive individuals. This effect lasted for up to 8 months and then began to stabilize.

Natural infection increases antibody levels

Otter noted, “Covid-19 antibody levels are elevated in people who were previously naturally infected and vaccinated, highlighting that vaccination provides an additional benefit for these individuals.”

Medscape asked Charlotte Thalin, PhD, an immunologist from Karolinska Institutet, Stockholm, Sweden, for comment on the study. Thålin studies a group similar to SIREN, called the Swedish Community Health Care Workers Group. “The new data from SIREN underscore the importance of the number of exposures to an antigen and the interval between them, whether exposure through vaccination or exposure through infection.”

“We see similar data in the Swedish community health-care worker cohort,” Thålin continued, “in which infection before vaccination leads to a twofold increase in antibodies, neutralizing amplitude, and T-cell responses, and a greater increase with a longer time interval between infection and vaccination.” “.

However, she cautioned that they are now seeing a higher rate of breakthrough infections of the Omicron vaccine, and this also applies to people with previous infections and three doses of the vaccine.

“As we approach a second booster dose – a fourth vaccine dose – we need to consider that many individuals have had up to five to six exposures to the antigen within a short time, sometimes within a year,” she noted. “This is a completely new scenario, with a lot of different combinations of vaccine and immunity triggered by infection. We don’t yet know the effect of these repeated immune exposures, and now we need to monitor immune responses after Omicron and booster doses more closely.”

SIREN originally aimed to understand how much protection people got after an initial infection and why they might get COVID-19 again. Otter explained that after the launch of the vaccination program in the UK, the protective effects of vaccination against COVID-19 were investigated as well as why some people became ill after vaccination.

In this latest analysis, Otter and colleagues evaluated anti-ligase antibodies in serum samples of a total of 5,871 health care workers, with 3,989 after one dose (at least 21 days) and 1,882 two doses (at least 14 days).

Most of the participants were women (82.3%) and white (87%) and came from all over the UK.

Participants were also categorized into those who had evidence of natural COVID-19 infection (confirmed by PCR testing or hypothesized due to their antibody profile) or those who were naïve to infection. Almost all (>99%) who naively contracted the infection were seroconverted after vaccination.

The primary outcome was anti-elevation antibody levels assessed according to dose, previous infection, dose interval, age, ethnicity, and comorbidities, including immunosuppressive diseases such as cancer of the immune system, rheumatic diseases, chronic respiratory diseases, diabetes, and obesity. , and chronic diseases. Neurological Disease.

In the infection-naive group, the mean anti-S titer (anti-S titer) was 75.48 BAU/mL after the first vaccine dose, and this increased to 7049.76 BAU/mL after the second dose.

The much higher antibody titer with the second dose in infection-naïve individuals, Otter said, “is what gives you the most protection, since the antibody titer is at its peak. Then it starts to gradually fade from that peak.”

In the post-infection group, the antibody titer also increased (2111.08 BAU/mL after the first dose and 16,052.39 BAU/mL after the second dose), although lower than that of the infection-naive group, due to additional exposure to infection, Otter added.

Antibody levels also varied according to the time elapsed between normal infection and dose 1 of vaccination. With a 3-month interval, antibody levels were 1970.83 (1506.01 – 2579.1) BAU/mL compared to 13759.31 (8097.78 – 23379.09) BAU/mL after a 9-month interval. Antibody levels after a single dose in the formerly infected are higher than in the naïve because “previous infection, then vaccination, is likely explained by T-cell expansion upon reinforcement by second exposure to the antigen, and then the response of mature memory B cells displayed for up to 6 months.” Otter explained.

Timing of 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 the increased prevalence of disease and the prevalence of worrisome variables,

More work is ongoing to understand the diminished immune response, the level of protection, and why some individuals develop COVID-19 even upon double vaccination.

Medscape asked Susanna Donacci, BMChB, Professor of Infectious Diseases, University of Oxford, UK, what the results of the timing interval for the fourth dose of the vaccine might mean across the UK population.

In the UK, fourth doses are given to people over 75 years of age, residents of elderly care homes, and those with compromised immune systems. “To make decisions about fourth doses for healthy people, we need to know how quickly antibody and T-cell responses are reduced,” said Donacci, who was part of the large SIREN study team but was not involved in the analysis that Otter led. “Current research suggests that the T-cell response may be better preserved than the antibody response, and less affected by variants such as Omicron.”

She explained the balance between antibodies and T-cell responses to vaccination. “Antibodies that neutralize the virus are likely to be important to prevent any infection at all, and unfortunately these antibodies fall in time, but T-cell responses are better sustained and help keep people away from the virus.” [the] She said.

Donacci added that it was necessary to wait and see what happens next with the development of SARS-CoV-2, as well as to wait for a longer follow-up after the third dose in healthy people. “Based on current evidence, it is my estimation that we are deferring decisions about IV doses in healthy people until late summer/fall.”

32nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID): Abstract 250. To be submitted on April 26, 2022.

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