Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)
Daniel J Sheward, Changil Kim, Roy A Ehling, Alec Pankow, Xaquin Castro Dopico, Darren Martin, Sai Reddy, Joakim Dillner, Gunilla B Karlsson Hedestam, Jan Albert, Ben Murrell
doi:10.1101/2021.12.19.473354
The recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in many countries, with a spike that is highly diverged from the pandemic founder, raising fears that it may evade neutralizing antibody responses. We cloned the Omicron spike from a diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus neutralization assay, sharing initial neutralization results only 13 days after the variant was first reported to the WHO, 8 days after receiving the sample. Here we show that Omicron is substantially resistant to neutralization by several monoclonal antibodies that form part of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference sera sampled shortly after infection or vaccination are substantially less potent against Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, neutralization of Omicron was low to undetectable. However, in recent samples from two cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to the pandemic founder variant, and some donors showing no loss at all. A similar pattern was observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing antibody responses by the Omicron variant, and suggest that increasing the magnitude of neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise titers to levels that are protective.
Author Contributions
Methods
Ethics statement HW and Convalescent cohorts: Informed consent was obtained from all participants as part of an ethics approval (Decision number 2020-01620, with amendments 2020-02881 and 2020-05630) from the Swedish Ethical Review Authority. BD cohort and the Omicron-positive sample from which the spike was cloned were anonymized, and not subject to ethical approvals, as per advisory statement 2020-01807 from the Swedish Ethical Review Authority.
Donor sample description Two cohorts were studied. Cohort 1 comprised serum samples with detectable neutralization against the Wu-Hu-1 founder variant from 17 anonymized blood donors ("BD"), donated during week 48, 2021, in Stockholm, Sweden. Cohort 2 comprised 17 serum samples from Hospital Workers ("HW") at the Karolinska University Hospital in Stockholm 20 , who were invited to participate in a study that aimed to characterize their antibody responses following SARS-CoV-2 infection and subsequent vaccinations. Participants, confirmed PCR positive, had serum sampled in April/May 2020, in June/July 2020 ("convalescent", prior to vaccination), and again in November 2021 ("HW"). Convalescent samples are from 9 unique donors, with 3 donors sampled in both April/May 2020 and June/July 2020. Statistical comparison was performed on the 9 samples from June/July 2020 only, to avoid non-independence due to repeated sampling of 3 donors. Supplementary Figure 4 ...
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'abstract': '<jats:p>The recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in '
'many countries, with a spike that is highly diverged from the pandemic founder, raising fears '
'that it may evade neutralizing antibody responses. We cloned the Omicron spike from a '
'diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus '
'neutralization assay, sharing initial neutralization results only 13 days after the variant '
'was first reported to the WHO, 8 days after receiving the sample. Here we show that Omicron '
'is substantially resistant to neutralization by several monoclonal antibodies that form part '
'of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference '
'sera sampled shortly after infection or vaccination are substantially less potent against '
'Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the '
'pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, '
'neutralization of Omicron was low to undetectable. However, in recent samples from two '
'cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were '
'prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust '
'cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to '
'the pandemic founder variant, and some donors showing no loss at all. A similar pattern was '
'observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. '
'Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize '
'Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing '
'antibody responses by the Omicron variant, and suggest that increasing the magnitude of '
'neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise '
'titers to levels that are protective.</jats:p>',
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