Longer Intervals Between COVID-19 Vaccine Doses Leads to Higher Antibody Levels

The current mRNA vaccines approved in the US, Pfizer-BioNTech and Moderna, both require 2 doses for a primary vaccination series. These doses are typically given 21 days apart for Pfizer-BioNTech, and at least 24 days apart for Moderna. However, new data suggests there may be benefits to waiting longer in between doses.

Research presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal, found a longer interval between COVID-19 vaccine doses can boost antibodies by 9-fold. The study, led by Dr. Ashley Otter of the UK Health Security Agency (UKHSA), sought to optimize the antibodies produced by vaccination to prevent the number of severe or fatal COVID-19 infections and prevent the virus from further mutating.

The investigators utilized the UK’s SIREN (SARS-CoV-2 Infection and Reinfection and EvaluatioN) study to identify nearly 6000 healthcare workers. These participants gave blood samples, which were measured for antibody levels. Participants received the Pfizer-BioNTech mRNA vaccine (BNT162b2).

Of the 5871 participants, 3989 had their first vaccine dose at least 21 days before the start of the study. 1882 healthcare workers had their second dose at least 14 days prior. Participants were categorized as either a history of COVID-19 infection (confirmed by PCR test or antibody profile), or infection naïve. Over 99% of participants who had not had previously had COVID-19 successfully seroconverted after vaccination.

After the first Pfizer-BioNTech dose, participants with prior infection had antibody levels up to 10 times higher than the naïve individuals; after dose 2, previously infected participants had antibody levels that averaged more than twice as high as those without prior infection.

Notably, infection naïve individuals with a longer interval between doses had antibody levels up to 9 times higher. Participants who received their second dose more than 2 weeks and less than 4 weeks after the first had antibody levels that averaged 1268.72, while infection naïve participants who received their second dose more than 10 weeks after the first averaged antibody levels of 11479.73. This observation was more pronounced in younger participants.

Longer dosing intervals did not significantly affect the healthcare workers who had previously contracted COVID-19. However, a longer interval between COVID-19 infection and the first vaccine dose was correlated with higher antibody levels.

The investigators noted that receiving a first vaccine dose 8 months after COVID-19 infection led to antibody levels 7 times higher than in those vaccinated 3 months after infection. This effect plateaued after 8 months, suggesting 8 months after an infection may be the ideal time for these individuals to receive their first vaccine dose.

Participants who were female and/or ethnic minorities had significantly higher post-vaccination antibody responses. Predictably, immunosuppressed persons had significantly lower post-vaccination antibody levels. Regardless of the time between infection and vaccination, all healthcare workers demonstrated a high antibody response to their second Pfizer-BioNTech vaccine dose.

This study, “Longer interval between COVID-19 vaccines generates up to nine times as many antibodies,” was presented during the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal, April 23-26, 2022.