More antibodies with longer intervals between COVID vaccine doses

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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 dose of the Pfizer/BioNTech vaccine (BNT162b2) in people without previous infection, according to UK government SIREN (SARS-CoV-2 Immunity and Reinfection Evaluation) data.

This interval-dependent antibody level varied by age, with those aged 45-54 showing an 11-fold increase with a longer dosing interval (greater than 10 weeks versus 2-4 weeks). People younger than 25 showed a 13-fold increase with the longer interval, but the number of participants was low in this subgroup.

Overall antibody levels in infection naïve participants were 1268.72 binding antibody units (BAU)/mL (1043.25 – 1542.91) in those with a 2-4 week interval from at 11,479.73 BAU/mL (10,742.78 – 12,267.24) (P < 0.0001), in those with an interval of at least 10 weeks between doses.

The work is the latest analysis from SIREN, which measured antibody levels in the blood of nearly 6,000 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 this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon.

In an interview with Medscape Medical NewsOtter 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 do not did not affect protection against infection”.

The study, published in the March issue of New England Journal of Medicinealso found that after the second dose of vaccine, there was an approximately 2.5-fold difference in antibody levels between those with a prior infection 16,052 (14,071-18,312) BAU/mL compared to 7,050 (6.634 – 7.491) BAU/mL in case of infection – naïve individuals (P < .0001).

After the first dose alone, antibody levels were up to 10 times higher in previously infected participants compared to infection-naïve individuals. This effect lasted for up to 8 months and then began to plateau.

Natural infection Increased antibody levels

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

Medscape asked Charlotte Thålin, PhD, an immunologist at the Karolinska Institute in Stockholm, Sweden, to comment on the study. Thålin is studying a cohort similar to SIREN, called the Swedish COMMUNITY Healthcare Worker Cohort. “The new data from SIREN underscores the importance of the number of antigen exposures and the time interval between them, whether exposure by vaccination or exposure by infection.”

“We see similar data in our cohort of Swedish COMMUNITY healthcare workers,” Thålin continued, “where pre-vaccination infection produces a more than two-fold improvement in antibodies, magnitude neutralization, and T-cell responses, and an even greater increase with a longer time interval between infection and vaccination.”

However, she warned that they are now seeing a high rate of breakthrough infections from the Omicron vaccine, and this is also true in people who have already been infected and have received three doses of the vaccine.

“As we approach a second booster – a fourth dose of vaccine – we must consider that many people will have had as many as five to six exposures to the antigen in a short period of time, sometimes within a year,” a- she pointed out. “This is a whole new scenario, with many different combinations of vaccine and infection-induced immunity. We don’t yet know the impact of these frequent immune exposures, and we now need to closely monitor immune responses after Omicron and booster doses. “

SIREN originally aimed to understand the degree of protection people have after developing a primary infection and why they might be re-infected with COVID-19. Following the rollout of the UK’s vaccination programme, the protective effects of vaccination against COVID-19 have been studied as well as the reasons why some people still get sick after being vaccinated, Otter said.

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 one dose (at least 21 days) and 1882 after two doses ( at least 14 days).

Most of the participants were female (82.3%) and of white ethnicity (87%) and came from across the UK.

Participants were also categorized into those who showed signs of natural COVID-19 infection (confirmed by a PCR test or suspected based on their antibody profile) or those who were naïve to infection. Almost all (>99%) of naïve infected persons were seroconverted after vaccination.

The primary outcome was anti-spike antibody levels assessed as a function of dose, previous infection, dosing interval, age, ethnicity, and comorbidities including immunosuppressive diseases such as cancers of the immune system, rheumatological diseases, chronic respiratory diseases, diabetes, obesity and chronic diseases. neurological disease.

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

The much higher antibody titer with the second dose in infection naïve individuals, “is what gives you the most protection, because your antibody titers are at their peak. They then begin to gradually decline from of this peak,” Otter said.

In the post-infection group, antibody titers also increased (2111.08 BAU/mL after the first dose and 16052.39 BAU/mL after the second dose), although less than in the naïve group. infection, due to the additional exposure to infection, Otter added.

Antibody levels also as a function of time elapsed between varied natural infection and dose 1 of vaccination. With a 3-month interval, antibody levels were 1970.83 (1506.01 – 2579.1) BAU/mL versus 13759.31 (8097.78 – 23379.09) BAU/mL after a 9 month interval. Antibody levels after one dose in previously infected people are higher than in people naïve to infection, because “previous infection and then vaccination is probably explained by T-cell expansion during ‘a boost with a second antigen exposure and then a maturing memory B cell response.’ which has been demonstrated for up to 6 months,” Otter explained.

Timing of fourth dose

As of March this year, 86.2% of the UK population aged over 12 had received at least two doses, but with the prevalence of the disease increasing and the spread of worrying variants, further work is needed. ongoing to understand the decline in immune response, level of protection and why some people develop COVID-19 even when double vaccinated.

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

In the UK, a fourth dose is given to people aged 75 and over, residents of elderly care homes and people with weakened immune systems. “To make decisions about fourth doses for healthy people, we need to see how quickly antibody and T-cell responses drop,” said Dunachie, who is part of the large SIREN study team but did not participate in the analysis conducted by Otter. “Current research suggests that the T cell response may be better maintained than the antibody response and less affected by variants like 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 these unfortunately fade over time, but the T cell responses are better sustained and help keep people out of harm’s way.” [the] the hospital,” she said.

Dunachie added that it was necessary to wait and see what happens next with the evolution of SARS-CoV-2, as well as to wait for longer follow-up after the third dose in healthy people. . “Based on the current evidence, my estimate is that we defer decisions on four doses in healthy people until late summer/fall.”

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

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