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Review
. 2022 Oct 20;10(10):1757.
doi: 10.3390/vaccines10101757.

Post-Vaccination Neutralization Responses to Omicron Sub-Variants

Henning Jacobsen  1 , Maeva Katzmarzyk  1 , Melissa M Higdon  2 , Viviana Cobos Jiménez  3 , Ioannis Sitaras  4 , Naor Bar-Zeev  2 , Maria Deloria Knoll  2
Affiliations
Review

Post-Vaccination Neutralization Responses to Omicron Sub-Variants

Henning Jacobsen et al. Vaccines (Basel). .

Abstract

Background: The emergence of the Omicron variant (B.1.1.529), which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera, raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Several clinically relevant sub-variants subsequently emerged rapidly.

Methods: We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform.

Results: Among 178 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 40.1-fold for BA.2.75; in boosted participants fold-reduction was similar for most sub-variants (5.3-fold to 7.0-fold); however, a more pronounced fold-change was observed for sub-variants related to BA.4 and BA.5 (10.4-fold to 14.2-fold). Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.4-fold) except for BA.4/5-related sub-variants which was higher (2.1-fold to 2.7-fold). Omicron sub-variant-specific responder rates were low post-primary vaccination (range median 28.0% to 65.9%) compared to the prototype (median 100%) but improved post-booster (range median 73.3% to 100%).

Conclusions: Fold-reductions in neutralization titers were comparable post-booster except for sub-variants related to BA.4 and BA.5, which had higher fold-reduction. Assessment after primary vaccination was not possible because of overall poor neutralization responses causing extreme heterogeneity. Considering large fold-decreases in neutralization titers relative to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against variants related to BA.4 or BA.5.

Keywords: COVID-19 vaccine; Omicron; SARS-CoV-2; neutralization; sub-variant.

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Conflict of interest statement

M.M.H. reports research grants from Pfizer for unrelated work; M.D.K. reports research grants from Pfizer and Merck and consultancy fees from Merck, all for unrelated work; N.B.-Z. reports research grants from Merck, from Johnson & Johnson and from Serum Institute of India, all for unrelated work; and consulting fees from Merck for unrelated work.

Figures

Figure 1
Figure 1
Overview of literature search and study selection process.
Figure 2
Figure 2
Fold-reduction in neutralization titers relative to the prototype strain for Omicron sub-variants. Primary (A,B) series vaccination or first boost vaccination (C,D), color coded by platform (A,C) or stratified for studies providing multiple variant-specific, paired observations (B,D). Every data point represents one observation. Median, IQR and group size is shown. n.d. no data.
Figure 3
Figure 3
Relative fold-reduction in neutralization titers across Omicron sub-variants. Reported fold-change in neutralization titers of Omicron sub-variants compared to Omicron BA.1 (A) and for each sub-variant to each-other (B). Only studies with at least two sub-variant specific and matched observations are shown. Median and IQR (upper right corner) and number of paired observations (lower left corner) is shown. n.d. = no data.
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