3 months of waiting after infection to get booster COVID19 shot can maximize increase in antibody levels

A new study found that a waiting period of 3 months for the third dose of mRNA vaccine elicits robust humoral immune response among those who typically had primary vaccination. The study results were published in the journal Clinical Infectious Diseases.  

COVID-19 mRNA vaccination has substantially mitigated the impact of the pandemic by preventing infection or attenuating disease severity. Despite several vaccine effectiveness studies, the waning of neutralizing antibodies after vaccination and a corresponding reduction in the protective effect against infection has been observed that questions the timing of the booster doses. Though the three doses elicited a robust immune response, there is limited data on the effectiveness of vaccines on SARS-CoV-2-affected individuals.  Hence researchers conducted a longitudinal study from a cohort of healthcare personnel (75.5%), first responders (4.6%), and other frontline workers (19.8%) in 6 US states, to assess antibody waning after dose-2, and response to dose-3, according to SARS-CoV-2 infection history. 

Sera were collected from the participants every three months, after SARS-CoV-2 infection, and after each COVID-19 vaccine, dose to test for antibodies. Three comparison groups were formed that included vaccine only with no known prior SARS-CoV-2 infection group with 224 participants; the infection before the dose-1 group with 123 participants; and the infection after dose-2 and before the dose-3 group with 41 participants. After testing sera, it was reported quantitatively as an area under the serial dilution curve (AUC). Using a linear mixed model changes in the AUC values over time were compared as fold changes. 

Key results of the study:

• About 388 participants who received dose-3 by November 2021 were analyzed.
• There was nearly an 8-month interval between dose 2 and dose 3.
• After dose 3, there was an increase in antibody levels to 2.5-fold (95%CI = 2.2-3.0) in group 2, and to 2.9-fold (95%CI = 2.6-3.3) in group 1.
• Those infected within 90 days before dose-3 (and median 233 days (IQR = 213-246) after dose-2) did not increase significantly after dose-3.

Thus, in patients with a waiting period of 3 months before the booster dose and post the SARS-CoV-2 infection, a robust humoral immune response was observed unlike those without a waiting period regardless of the primary vaccination. 

Further reading: Herring MK, Romine JK, Wesley MG, et al. SARS-CoV-2 infection history and antibody response to three COVID-19 mRNA vaccine doses [published online ahead of print, 2022 Dec 29]. Clin Infect Dis. 2022;ciac976. doi:10.1093/cid/ciac976