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
Authors: Medigeshi Guruprasad , Batra Gaurav , Murugesan Deepika Rathna , Thiruvengadam Ramachandran , Chattopadhyay Souvick , Das Bhabatosh , Gosain Mudita , Ayushi  , Singh Janmejay , Anbalagan Ananthraj , Shaman Heena , Pargai Kamal , Mehdi Farha , Das Soon Jyoti , Kahlon Namrata , Singh Savita , Kshetrapal Pallavi , Wadhwa Nitya , Pandey Anil K , Bhatnagar Shinjini , Garg Pramod Kumar 
Published: January 2022

AbstractBackgroundRapid 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.MethodsWe 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.FindingsThe 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) suggesting better neutralization in those with prior infection. The 50% neutralisation 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].InterpretationOmicron 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.FundingDBT, India; GIISER-BMGF, USAResearch in contextEvidence before this studyThe Omicron variant of SARS-CoV-2 is fast becoming the dominant circulating strain world-wide. We did a literature search on PubMed between 01 November 2020 to 04 January 2022 using the terms “Omicron” and “neutralisation” and found 11 results for virus neutralisation against omicron by vaccine/natural infection induced antibodies. We identified two published and one preprint articles relevant to omicron virus neutralisation using live virus neutralization. Preliminary reports suggest that omicron variant is significantly less susceptible to in-vitro neutralisation by antibodies among recipients of mRNA vaccines (BNT162b2 and mRNA-1273), adenovirus vectored vaccine (ChAdOx1 nCoV-19 vaccines) and no virus neutralization was observed in subjects who received Coronavac (inactivated virus vaccine). Data regarding immune escape among those with natural SARS-CoV2 infection and vaccination are not available.Added value of this studyWe report here that the proportion of neutralisers (those who demonstrated a FRNT50 titre >1:20) was significantly reduced against the omicron variant as compared to the ancestral and delta variant. The geometric mean titre of neutralisation among the vaccinated individuals without a history of previous natural infection was significantly reduced against the omicron variant as compared with ancestral and delta variants. The titres among the those with a history of previous infection also followed the same pattern, but the neutralising ability was better in them than those who did not have previous infection.Implications of all the available evidenceOmicron variant of SARS-CoV-2 is capable of escaping immunity provided by currently available vaccines and even natural infection due to significant mutations in its spike protein. The drop in neutralisation might be alarming, but the real-world impact of these reduced neutralisation titres on major public health indices like hospitalisation rates and mortality rates have to be interpreted along with the other factors such as inherent pathogenicity of the variant, immunization uptakes and seroprevalence from natural infection in different geographical regions and the expected role of cellular immune responses to the variant. Our data may guide policy on booster vaccination to deal with an impending public health emergency as a result of surge in omicron cases.