Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

Abstract

Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT₅₀ of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

Figure 1:. Enhancement of Delta neutralization by Omicron infection.

(A) Neutralization of Omicron virus by Omicron infection elicited plasma in n=10 convalescent vaccinated participants, (n=5 two doses of Pfizer BNT162b2, n=5 Johnson and Johnson Ad26.CoV2.S). Each participant was sampled at the initial enrollment visit (median 5 days post-symptom onset) and compared to the last follow-up visit (median 23 days post-symptom onset). Numbers are geometric mean titers (GMT) of the reciprocal plasma dilution (FRNT₅₀) resulting in 50% neutralization. Fold-change is calculated by dividing the larger GMT value by the smaller value and arrows indicate direction of change between enrollment and follow-up. Dashed line is most concentrated plasma tested. (B) as in (A) for the n=13 unvaccinated participants. (C) Neutralization of Delta virus by Omicron infection elicited plasma in the vaccinated participants. (D) as in (C) for the unvaccinated participants. (E) Neutralization of Omicron compared to Delta virus by Omicron infection elicited plasma in vaccinated participants at the last follow-up visit. Arrow indicates direction of change between Omicron and Delta virus. (F) as in (E) for the unvaccinated participants. p-values were: (A) 6.6 ×10⁻⁴, (B) 0.031, (C) 2.3 ×10⁻³, (D) 0.15, (E) 0.032, (F) 0.79 as determined by the Wilcoxon rank sum test.

Figure 2:. Omicron and Delta neutralization capacity over time in Omicron infected participants.

Neutralization of Omicron (blue) and Delta (red) at all study visits. Participant number is as in Table S3. First row are Pfizer BNT162b2 vaccinated, second row are Johnson and Johnson Ad26.CoV2.S vaccinated, and bottom three rows are unvaccinated participants. X-axis is the time post-symptom onset when sample was collected, and y-axis is neutralization as FRNT₅₀. Dashed line is the most concentrated plasma tested.

Figure 3:. Escape of Omicron virus from Delta infection elicited immunity.

Neutralization of Delta compared to Omicron virus by Delta infection elicited plasma immunity in vaccinated and unvaccinated participants. 18 samples were tested from n=14 participants infected during the Delta infection wave in South Africa (see Table S4). Dashed line is the most concentrated plasma tested. p-value is 1.6 × 10⁻⁷ as determined by the Wilcoxon rank sum test.