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Omicron subvariant BA.2 circulation is rapidly increasing globally.


We evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.


Using 50% plaque reduction neutralisation tests (PRNT), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.


In vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT titres were comparable but significantly (p < 10 − 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.


Existing vaccines can be of help against the BA.2 subvariant.


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  1. World Health Organization (WHO). Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Geneva: WHO; 2021. Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern
  2. Desingu PA, Nagarajan K, Dhama K. Emergence of Omicron third lineage BA.3 and its importance. J Med Virol. 2022;94(5):1808-10.  https://doi.org/10.1002/jmv.27601  PMID: 35043399 
  3. Lyngse FP, Mortensen LH, Denwood MJ, Christiansen LE, Møller CH, Skov RL, et al. Transmission of SARS-CoV-2 Omicron VOC subvaraints BA.1 and BA.2: Evidence from from Danish households. medRxiv doi: (2022). https://doi.org/10.1101/2021.12.27.21268278 
  4. Wolter N, Jassat W, Walaza S, Welch R, Moultrie H, Groome M, et al. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study. Lancet. 2022;399(10323):437-46.  https://doi.org/10.1016/S0140-6736(22)00017-4  PMID: 35065011 
  5. Mallapaty S, Callaway E, Kozlov M, Ledford H, Pickrell J, Van Noorden R. How COVID vaccines shaped 2021 in eight powerful charts. Nature. 2021;600(7890):580-3.  https://doi.org/10.1038/d41586-021-03686-x  PMID: 34916666 
  6. Cheng SMS, Mok CKP, Leung YWY, Ng SS, Chan KCK, Ko FW, et al. Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination. Nat Med. 2022;28(3):486-9.  https://doi.org/10.1038/s41591-022-01704-7  PMID: 35051989 
  7. Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med. 2022;28(3):481-5.  https://doi.org/10.1038/s41591-022-01705-6  PMID: 35051990 
  8. Waltz E. Does the world need an Omicron vaccine? What researchers say. Nature. 2022;602(7896):192-3.  https://doi.org/10.1038/d41586-022-00199-z  PMID: 35091718 
  9. UK Health Security Agency. SARS-CoV-2 variants of concern and variants under investigation in England. Technical briefing 35. 28 Jan 2022. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050999/Technical-Briefing-35-28January2022.pdf
  10. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205-11.  https://doi.org/10.1038/s41591-021-01377-8  PMID: 34002089 
  11. Keeton R, Richardson SI, Moyo-Gwete T, Hermanus T, Tincho MB, Benede N, et al. Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner. Cell Host Microbe. 2021;29(11):1611-1619.e5.  https://doi.org/10.1016/j.chom.2021.10.003  PMID: 34688376 
  12. Mok CKP, Cohen CA, Cheng SMS, Chen C, Kwok KO, Yiu K, et al. Comparison of the immunogenicity of BNT162b2 and CoronaVac COVID-19 vaccines in Hong Kong. Respirology. 2022;27(4):301-10.  https://doi.org/10.1111/resp.14191  PMID: 34820940 
  13. Mok CKP, Chen C, Yiu K, Chan TO, Lai KC, Ling KC, et al. A Randomized Clinical Trial Using CoronaVac or BNT162b2 Vaccine as a Third Dose in Adults Vaccinated with Two Doses of CoronaVac. Am J Respir Crit Care Med. 2022;205(7):844-7.  https://doi.org/10.1164/rccm.202111-2655LE  PMID: 35015969 
  14. Matsuyama S, Nao N, Shirato K, Kawase M, Saito S, Takayama I, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci USA. 2020;117(13):7001-3.  https://doi.org/10.1073/pnas.2002589117  PMID: 32165541 
  15. Lau EHY, Hui DS, Tsang OT, Chan WH, Kwan MY, Chiu SS, et al. Long-term persistence of SARS-CoV-2 neutralizing antibody responses after infection and estimates of the duration of protection. EClinicalMedicine. 2021;41:101174.  https://doi.org/10.1016/j.eclinm.2021.101174  PMID: 34746725 
  16. Cromer D, Steain M, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2022;3(1):e52-61.  https://doi.org/10.1016/S2666-5247(21)00267-6  PMID: 34806056 
  17. Iketani S, Liu L, Guo Y, Liu L, Chan JF, Huang Y, et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature. 2022; 604(7906):553-6.  https://doi.org/10.1038/s41586-022-04594-4  PMID: 35240676 
  18. McCallum M, Czudnochowski N, Rosen LE, Zepeda SK, Bowen JE, Walls AC, et al. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement. Science. 2022;375(6583):864-8.; Epub ahead of print.  https://doi.org/10.1126/science.abn8652  PMID: 35076256 
  19. Harvey WT, Carabelli AM, Jackson B, Gupta RK, Thomson EC, Harrison EM, et al. , COVID-19 Genomics UK (COG-UK) Consortium. SARS-CoV-2 variants, spike mutations and immune escape. Nat Rev Microbiol. 2021;19(7):409-24.  https://doi.org/10.1038/s41579-021-00573-0  PMID: 34075212 
  20. Liu Y, Soh WT, Kishikawa JI, Hirose M, Nakayama EE, Li S, et al. An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies. Cell. 2021;184(13):3452-3466.e18.  https://doi.org/10.1016/j.cell.2021.05.032  PMID: 34139176 
  21. Yamasoba D, Kimura I, Nasser H, Morioka Y, Nao N, Ito J, et al. Virological characteristics of SARS-CoV-2 BA.2 variant.2022. February152022, bioRxiv2022.02.14.480335; doi:  https://doi.org/10.1101/2022.02.14.480335 
  22. Mykytyn AZ, Rissmann M, Kok A, Rosu M, Schipper D, Breugem TI, et al. Omicron BA.1 and BA.2 are antigenically distinct SARS-CoV-2 variants. Preprint. bioRxiv. 2022 https://doi.org/10.1101/2022.02.23.481644 
  23. McMenamin ME, Nealon J, Lin Y, Wong JY, Cheung JK, Lau EHY, et al. Vaccine effectiveness of two and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong. Preprint. medRxiv.
  24. Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months. N Engl J Med. 2021;385(24):e84.  https://doi.org/10.1056/NEJMoa2114583  PMID: 34614326 
  25. Zeng G, Wu Q, Pan H, Li M, Yang J, Wang L, et al. Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials. Lancet Infect Dis. 2022;22(4):483-95.  https://doi.org/10.1016/S1473-3099(21)00681-2 
  26. Wratil PR, Stern M, Priller A, Willmann A, Almanzar G, Vogel E, et al. Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. Nat Med. 2022;28(3):496-503.  https://doi.org/10.1038/s41591-022-01715-4  PMID: 35090165 
  27. Pilz S, Theiler-Schwetz V, Trummer C, Krause R, Ioannidis JPA. SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity. Environ Res. 2022;209:112911.  https://doi.org/10.1016/j.envres.2022.112911  PMID: 35149106 
  28. Gov.UK Coronavirus (COVID-19) in the UK. Updated Wednesday 27 April 2022. [Accessed: 28 Apr 2022]. Available from: https://coronavirus.data.gov.uk/details/cases
  29. Swadling L, Diniz MO, Schmidt NM, Amin OE, Chandran A, Shaw E, et al. , COVIDsortium Investigators. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2022;601(7891):110-7.  https://doi.org/10.1038/s41586-021-04186-8  PMID: 34758478 
  30. Gao Y, Cai C, Grifoni A, Müller TR, Niessl J, Olofsson A, et al. Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nat Med. 2022;28(3):472-6.  https://doi.org/10.1038/s41591-022-01700-x  PMID: 35042228 

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