Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination

This study investigates the antibody response of an individual who was infected with two different Omicron subvariants — BA.1 10 weeks after receiving the third COVID-19 vaccine dose and BA.2 13 weeks later. The participant’s immune response was compared to 124 individuals who did not experience SARS-CoV-2 infection and had received three vaccine doses. The goal of the study was to understand how well the immune system responds to sequential SARS-CoV-2 infections with these closely related variants.

The participant was a 30-year-old healthcare worker who did not have any major health concerns. The participant received three doses of mRNA vaccine (all Pfizer monovalent; 30 mcg) in late December 2020, early February 2021, and late October 2021. The comparison group was 74% female with a median age of 57 years.

Key Findings:

• One month after the second and third vaccine doses, the participant’s antibody levels and neutralization activities were average compared to other COVID-19-naive individuals who had received three doses. These results indicate that the participant’s overall vaccine responses were typical of the cohort, but nevertheless insufficient to prevent infection by BA.1 approximately six weeks later.
• The first Omicron infection significantly boosted the participant’s immune response, placing the antibody levels and virus neutralization ability in the top 5% of the comparison group. Nevertheless, this boost was insufficient to prevent reinfection by BA.2 approximately 10 weeks later.
• The second infection only modestly increased the immune response to both BA.1 and BA.2 variants.
• Despite BA.1 infection and BA.2 reinfection, the participant’s virus neutralization activity against BA.1 one month after the third dose, which represented the highest activity measured during the study, remained four-fold lower compared to that against the wild-type strain one-month post-third vaccine dose. The substantially weaker ability of even “hybrid” (vaccine and dual-infection induced) immune responses to neutralize Omicron compared to wild-type suggests that the participant may remain at risk of additional Omicron infection.

Overall, the study highlights that while COVID-19 vaccines are effective in preventing severe disease, they may not completely protect against infections with different Omicron subvariants. This is particularly important as immune responses from vaccines naturally decline over time. Therefore, it remains crucial to maintain additional protective measures, such as mask-wearing and social distancing, to mitigate the spread of these highly immune-evasive variants.

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