Omicron infection enhances Delta antibody immunity in vaccinated persons.

The extent to which Omicron infection1-9, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement.

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

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.