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COVID-19 vaccine effectiveness is reduced against Omicron sub-variants, especially BA.4 and BA.5. Booster doses improve neutralization but significant reductions persist, indicating lower protection against infection and disease.

Keywords:
COVID-19 vaccineOmicronSARS-CoV-2neutralizationsub-variant

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Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • The Omicron variant (B.1.1.529) and its sub-variants have raised concerns regarding COVID-19 vaccine effectiveness due to significant reductions in neutralization capacity.
  • Rapid emergence of clinically relevant Omicron sub-variants necessitates an evaluation of vaccine-induced immune responses.

Purpose of the Study:

  • To evaluate the reduction in SARS-CoV-2 neutralization capacity against Omicron sub-variants after primary vaccination and booster doses.
  • To compare neutralization capacity across different Omicron sub-variants and vaccine platforms.

Main Methods:

  • Systematic review and meta-analysis of published and pre-print studies reporting neutralization data.
  • Calculation of median fold-reduction in neutralization capacity compared to the prototype strain and between sub-variants.
  • Analysis of responder rates post-primary vaccination and post-booster doses.

Main Results:

  • Fold-reduction in neutralization capacity varied widely by sub-variant after primary vaccination (e.g., 4.2-fold for BA.3 to 40.1-fold for BA.2.75).
  • Boosted participants showed similar fold-reductions for most sub-variants (5.3-fold to 7.0-fold), but higher reductions for BA.4/BA.5-related sub-variants (10.4-fold to 14.2-fold).
  • Responder rates were low post-primary vaccination (28.0%–65.9%) but improved significantly post-booster (73.3%–100%).

Conclusions:

  • Neutralization titers showed comparable fold-reductions post-booster, except for BA.4/BA.5-related sub-variants, which exhibited higher fold-reductions.
  • Primary vaccination alone resulted in poor and heterogeneous neutralization responses, making assessment difficult.
  • Reduced vaccine effectiveness against all Omicron sub-variants, particularly BA.4/BA.5, is highly likely due to significant decreases in neutralization titers.