COVID-19 primary series and booster vaccination and immune imprinting

Laboratory science evidence suggests possibility of immune imprinting, a negative impact for vaccination on subsequent protective immunity against SARS-CoV-2 infection. We investigated differences in incidence of SARS-CoV-2 reinfection in the cohort of persons who had a primary omicron infection, but different vaccination histories using matched, national, retrospective, cohort studies. Adjusted hazard ratio (AHR) for incidence of reinfection, factoring also adjustment for differences in testing rate, was 0.43 (95% CI: 0.39-0.49) comparing history of two-dose vaccination to no vaccination, 1.47 (95% CI: 1.23-1.76) comparing history of three-dose vaccination to two-dose vaccination, and 0.57 (95% CI: 0.48-0.68) comparing history of three-dose vaccination to no vaccination. Divergence in cumulative incidence curves increased markedly when incidence was dominated by BA.4/BA.5 and BA.2.75* omicron subvariant. History of primary-series vaccination enhanced immune protection against omicron reinfection, but history of booster vaccination compromised protection against omicron reinfection. These findings do not undermine the short-term public health utility of booster vaccination. TeaserHistory of booster vaccination showed lower protection against omicron reinfection than history of two-dose vaccination.