The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be highly transmissible and to evade neutralizing antibody immunity induced by vaccination and prior SARS-CoV-2 infection. Omicron infections are quickly spreading worldwide, often in the face of high Delta variant infection levels.

Study: Omicron infection enhances neutralizing immunity against the Delta variant. Image Credit: Dmitry Demidovich/Shutterstock

In this paper, researchers studied whether the neutralizing immunity produced by Omicron also increases neutralizing immunity of the Delta variant. In the Omicron infection wave in South Africa, the authors enrolled both previously vaccinated and unvaccinated people who were infected with SARS-CoV-2 shortly after symptom onset.

The authors then tested the participant's ability to neutralize both Omicron and Delta at the time of enrolment and 14 days later. Over this time, Omicron neutralization increased 14-fold, indicating a growing antibody response to the variation. There was a significant rise in Delta neutralization, which increased 4.4-fold.

Delta's capacity to re-infect persons infected with Omicron may be harmed due to increased Delta variant neutralization. With new evidence indicating that Omicron is less pathogenic than Delta at this stage in the pandemic, such an outcome could be beneficial in terms of lowering the coronavirus disease 2019 (COVID-19) burden of severe disease.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* server.

The study

The authors wanted to see if Omicron infection caused neutralizing immunity against the Delta variant. The Omicron virus lacking the R346K mutation was isolated from a South African infection. The neutralization escape of this virus was identical to that of a previous Omicron isolate with the R346K mutation.

The authors neutralized this isolate using plasma from 15 people enrolled during the Omicron infection wave in South Africa, and each of them had a confirmed SARS-CoV-2 diagnosis by qPCR. Live viral neutralization assay to calculate the focus reduction neutralization test (FRNT50) value was used, which is the inverse of the plasma dilution required to reduce infection foci by 50%.

The bulk of the recruited participants' infecting viruses was successfully sequenced, and they were all Omicron. Although 11 of the 15 individuals were admitted to the hospital due to COVID-19 symptoms, none required supplemental oxygen. Participants were sampled at enrolment, which was a median of 4 days after symptom onset and again at a median of 14 days after enrolment.

Two subjects were eliminated from the study because they could not neutralize Omicron at either timepoint. Two of the remaining 13 subjects had no detectable SARS-CoV-2 at the time of enrolment, indicating that illness had already cleared and that they were collected later after infection. Seven of the 13 individuals were vaccinated, three with two doses of Pfizer-BNT162b2 and four with Johnson & Johnson Ad26.CoV2.S vaccines, one of which was boosted with a second dose of Ad26.CoV2.S.

The authors found that Omicron neutralization increased from a low geometric mean (GMT) FRNT50 of 20 to 285, a 14.4-fold increase between enrolment and the later visit. Importantly, Delta neutralization increased 4.4-fold over this time, from FRNT50 of 80 to 354.

Both Omicron and Delta virus neutralization values were quite high before enrolment for the two people who were presumably sampled at a longer time post-infection. They did not increase significantly with time, indicating that neutralization capacity plateaued before enrolment.

When comparing Omicron and Delta neutralization at the most recent time point, it was discovered that vaccinated participants were better able to mount a neutralizing response against the Delta virus. Still, unvaccinated participants' responses were more varied.

Each variant's ability to elicit immunity that can cross-neutralize another variant differs. Delta-induced immunity does not cross-neutralize the Beta virus, while Beta-induced immunity does not cross-neutralize Delta very efficiently.

Participants in this study, on the other hand, were almost certainly already infected, and more than half were vaccinated. As a result, it's unclear whether the authors observed successful Delta virus cross-neutralization by Omicron elicited antibodies or antibody immunity from past infection and/or vaccination.

Implications

These findings support Omicron displacing the Delta variant because it can elicit immunity that neutralizes Delta, making re-infection with Delta less likely. On the other hand, Omicron avoids the neutralizing immunity elicited by Delta and thus has the potential to re-infect Delta-infected individuals.

The implications of such a shift would be determined by whether Omicron is truly less pathogenic than Delta. If this is the case, the incidence of COVID-19 severe disease will be reduced, and the infection will be less disruptive to individuals and society.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.