Longer COVID vaccine dose interval tied to higher antibody levels

COVID vaccine center sign in England
COVID vaccine center sign in England

Tim Dennell / Flickr cc

An interval of over 10 weeks between COVID-19 vaccine doses was associated with SARS-CoV-2 antibody levels up to 11 times higher than with an interval of 2 to 4 weeks in never-infected participants, according to a preprint paper to be presented at the upcoming annual congress of the European Society of Clinical Microbiology & Infectious Diseases (ESCMID).

The meeting starts tomorrow in Lisbon, Portugal.

Researchers from the UK Health Security Agency (HSA) measured antibody levels in blood samples from nearly 6,000 healthcare workers who received two doses of the Pfizer/BioNTech COVID-19 vaccine. Participants were enrolled in the UK's SARS-CoV-2 Infection and Reinfection and EvaluatioN (SIREN) study, according to an ESCMID press release issued yesterday.

Of the 5,871 participants, 3,989 received their first vaccine dose at least 21 days earlier, and 1,882 received their second dose at least 14 days before. Some vaccinees had previously tested positive for COVID-19.

Women, ethnic minorities had strongest response

Over 99% of never-infected participants had detectable antibodies after vaccination. After the first dose, previously infected participants' antibody levels were up to 10 times higher than those of their COVID-naïve counterparts. After the second dose, previously infected participants' antibody levels were upwards of twice as high as their never-infected peers.

A longer interval between vaccine doses (over 10 weeks vs 2 to 4 weeks) was tied to antibody levels—as measured by geometric mean anti-S titers—up to 11 times higher in COVID-naïve participants, across all age-groups. While the dosing interval didn't factor into antibody levels in previously infected participants, a longer time between infection and vaccination was associated with higher antibody concentrations.

Antibody levels in vaccine recipients who had their first dose 8 months after infection were seven times higher than in those vaccinated 3 months post-infection. Concentrations leveled off after 8 months, which the study authors said suggests that 8 months after infection may be an ideal time for the first vaccine dose in this group. But regardless of timing between infection and vaccination, all participants had a very high antibody response after the second dose.

Women and ethnic minorities had significantly higher antibody concentrations after vaccination, while those with impaired immune systems mounted significantly lower antibody responses.

Extending vaccine intervals

The study authors concluded, "Anti-S titres were much higher after two vaccine doses than infection alone … with longer intervals between successive vaccine doses, or first vaccine dose after infection, associated with an increased antibody response as demonstrated by others."

They also highlighted the need of vaccinating already-infected people, noting, "Other studies have also found higher anti-S titres following two antigen exposures, whether vaccination alone or infection and then a single vaccine dose, but few have shown that those with prior infection continue to have higher titres than double-vaccinated infection naïve individuals, suggesting that those with prior infection still benefit from vaccination."

First author Ashley David Otter, PhD, technical lead for SAR-CoV-2 immunology at the HSA, said in the release that the study strongly supports lengthening the interval between COVID-19 vaccine doses. "However, further research is needed to determine whether these higher antibody levels provide greater protection against COVID-19 disease and how this longer dosing interval may affect booster responses," he said.

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