Sub-optimal Neutralisation of Omicron (B.1.1.529) Variant by Antibodies induced by Vaccine alone or SARS-CoV-2 Infection plus Vaccine (Hybrid Immunity) post 6-months

Abstract

Background: Rapid expansion of the omicron SARS-CoV-2 variant of concern despite extensive vaccine coverage might be related to decreased neutralising ability of vaccine induced antibodies. The neutralising ability of different vaccines with or without natural SARS-CoV-2 infection against omicron is however not well known. Methods: We tested the ability of vaccine and natural infection induced antibodies to neutralise omicron variant in a live virus neutralisation assay. Four groups of individuals were included: (i) complete vaccination with ChAdOx1 nCoV-19 (n=20), (ii) complete vaccination with ChAdOx1 nCoV-19 plus prior SARS-CoV-2 infection during the delta variant driven surge (n=20), (iii) complete vaccination with inactivated whole virus vaccine (BBV152) (n=20), (iv) complete vaccination with BBV152 plus prior SARS-CoV-2 infection (n=20). Primary outcome was fold-change in the virus neutralisation ability of plasma against the omicron variant compared with ancestral and delta variant. Findings: The neutralisation geometric mean titre (GMT) was 384 (95% CI: 662, 223) against the ancestral virus with BBV152 vaccination alone and 383 (95% CI: 709, 207) with ChAdOx1 nCov-19 vaccination alone. The corresponding values for hybrid immunity groups were 795 (95% CI: 1302, 486) and 1424 (95% CI: 2581,786) respectively. Against the omicron variant, only 5 out of 20 in both BBV152 and ChAdOx1 nCoV-19 vaccine only groups, 5 out of 19 in BBV152 plus SARS-CoV-2 infection group, and 9 out of 20 in ChAdOx1 nCoV-19 plus SARS-CoV-2 infection group exhibited neutralisation titres above the lower limit of quantification (1:20). The 50% neutralization titre against ancestral strain and omicron demonstrated strong correlation with anti-RBD IgG levels [Pearson r: 0.94 (0.91, 0.96) p: <0.001 and 0.92 (0.88, 0.95) p:<0.001 respectively]. Interpretation: Omicron variant shows significant reduction in neutralising ability of both vaccine induced and hybrid immunity induced antibodies which might explain immune escape and high transmission even in the presence of widespread vaccine coverage.

Antibody response after a single dose of BBV152 vaccine negatively correlates with pre-existing antibodies and induces a significant but low levels of neutralizing antibodies to Omicron variant

“…We observed a clear negative correlation between the baseline FRNT50 titer for delta variant and the fold change in titer values after a single dose of vaccination (Figure 1E). While this study was in progress, omicron (B.1.1.529) emerged as a variant of concern and antibodies from most vaccines showed reduced efficiency in neutralizing this 10 variant 7,11,12 . We randomly selected 55 paired samples (which had a FRNT50 value for the delta variant) to test for their ability to neutralize the omicron variant.…”

“…SARS-CoV-2 Omicron isolate (sub-lineage BA.1) was obtained from Leo Poon 6 . SARS-CoV-2 variants were propagated in Vero E6 cells or Calu-3 cells 7 and virus passaging was limited to four passages. All virus stocks used in this study was verified by whole genome sequencing using total RNA sample of the culture on Nanopore sequencing platform as described previously to confirm the variant 8 .…”

“…Virus microneutralization assay by focus reduction neutralization titer assay using indicating virus isolates was performed as described earlier with minor modifications in omicron variant staining 7 . Briefly, serum samples were serially diluted from 1:20 to 1:640 and virus neutralization was tested in Vero E6 cells.…”

SARS-CoV-2 variants’-Alpha, Delta, and Omicron D614G and P681R/H mutations impact virus entry, fusion, and infectivity

“…The current available vaccines are targeted to spike domain which is the most immunogenic region. The introduction of new mutations in the SARS-CoV-2 virus is mainly in the spike domain, which is resulting in immune escape and drastic reduction in neutralization e cacy to current vaccines 37,[39][40][41] . Hence, it is utmost important to understand the virus entry and fusion mechanism of emerging variants.…”

“…3). In contrast, Omicron live virus does not produce cytopathic effect in Vero E6 and for in vitro studies, Omicron live viruses are grown in Calu-3 cells 37 . Vero E6 cells are de cient in ACE2 and TMPRSS2 receptors, which might be the reason of slow growth of variants and less CPE in Vero E6 cell line as compared to ancestral virus which could non-speci cally enter the Vero E6 cells 38 .…”