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   XPost: alt.government.abuse, alt.politics.democrats, mi.misc   
   From: democrats-suck@twitter.com   
      
   TO THE EDITOR:   
      
   The newly emerged B.1.1.159 (omicron) variant of severe acute   
   respiratory syndrome coronavirus 2 (SARS-CoV-2)1 has a large number   
   of changes — 32 — in its spike protein relative to that of the   
   original virus (Wuhan-hu-1), particularly in the receptor-binding   
   domain and the N-terminal domain, the primary targets of   
   neutralizing antibodies. Previously, we showed that approximately 20   
   changes introduced into a synthetic polymutant spike protein (PMS20)   
   are sufficient for substantial evasion of the polyclonal   
   neutralizing antibodies elicited in the majority of persons who have   
   recovered from coronavirus disease 2019 (Covid-19) or have received   
   two doses of an mRNA vaccine.2 Of note, several changes in the PMS20   
   spike protein are the same as or similar to changes in the omicron   
   variant (Fig. S1 in the Supplementary Appendix, available with the   
   full text of this letter at NEJM.org).   
      
   We measured neutralizing antibody titers against Wuhan-hu-1, PMS20,   
   and omicron spike pseudotypes in 169 plasma specimens from 47   
   persons with diverse exposures to SARS-CoV-2 antigens through   
   infection, vaccination, or both (see Supplementary Methods and   
   Tables S1, S2, and S3).3-5 In plasma specimens obtained at   
   approximately 1 month and 6 months after infection from persons who   
   had recovered from Covid-19, the 50% neutralization titer (NT50)   
   values were a mean (±SD) of 60±47 and 37±27 times lower for PMS20   
   than for Wuhan-hu-1, respectively, and 58±51 and 32±23 times lower   
   for omicron than for Wuhan-hu-1 (Fig. S2A and S2B). Similarly,   
   plasma specimens obtained from different persons in the same cohort   
   1 year after infection had NT50 values that were 34±24 times lower   
   for PMS20 and 43±23 times lower for omicron than for Wuhan-hu-1   
   (Fig. S2C).   
      
   In plasma specimens from persons who had received two doses of an   
   mRNA vaccine (BNT162b2 [Pfizer–BioNTech] or mRNA-1273 [Moderna]) 1.3   
   months before sampling, the NT50 values were 187±24 times lower for   
   PMS20 and 127±66 times lower for omicron than for Wuhan-hu-1 (Fig.   
   S3A). At 5 months after vaccination, the neutralization potency was   
   58±23 times lower for PMS20 and 27±17 times lower for omicron (Fig.   
   S3B). Many plasma specimens from recipients of the single-dose   
   Ad26.COV2.S vaccine (Johnson & Johnson–Janssen), obtained 1 or 5   
   months after vaccination, lacked detectable neutralizing activity   
   against PMS20 or omicron (Fig. S3C and S3D), which precluded a   
   meaningful quantitative assessment of variant-specific differences.   
      
   Of note, however, vaccination of persons who had recovered from   
   Covid-19 or administration of a third dose of an mRNA vaccine to   
   vaccinated persons at least 6 months after the second dose of an   
   mRNA vaccine led to a substantial gain in neutralizing activity   
   against PMS20 and omicron (Fig. S4). Specifically, after vaccination   
   in persons who had previously been infected with SARS-CoV-2, the   
   NT50 values were 238 times, 214 times, and 154 times greater for   
   Wuhan-hu-1, PMS20, and omicron pseudotypes, respectively, than the   
   prevaccination convalescent-phase titers in the same persons (Figure   
   1A). For those who had received two doses of an mRNA vaccine   
   approximately 6 months earlier and then received a third dose of an   
   mRNA vaccine approximately 1 month before sampling, the NT50 values   
   after the booster dose were 26 times greater for Wuhan-hu-1, 35   
   times greater for PMS20, and 38 times greater for omicron (Figure   
   1B). Neutralizing titers against omicron were substantial (ranging   
   from 1411 to 56,537) in all persons who had had Covid-19 and were   
   then vaccinated and in those who had received three doses of an mRNA   
   vaccine, but titers were low or undetectable in many unvaccinated   
   persons who had had Covid-19 and in recipients of only two doses of   
   an mRNA vaccine (Figure 1).   
      
   Although these findings indicate that the omicron variant shows an   
   unprecedented degree of neutralizing antibody escape, they also   
   suggest that boosting and promoting affinity maturation of   
   antibodies in persons who have previously been infected or   
   vaccinated,4,5 with the use of existing Wuhan-hu-1–based vaccine   
   immunogens, will provide additional protection against infection   
   with the omicron variant and subsequent disease.   
      
   Fabian Schmidt, Ph.D.   
   Frauke Muecksch, Ph.D.   
   Yiska Weisblum, Ph.D.   
   Justin Da Silva, M.Sc.   
   Eva Bednarski, B.Sc.   
   Alice Cho, Ph.D.   
   Zijun Wang, M.D., Ph.D.   
   Christian Gaebler, M.D.   
   Marina Caskey, M.D.   
   Michel C. Nussenzweig, M.D., Ph.D.   
   Theodora Hatziioannou, Ph.D.   
   Paul D. Bieniasz, Ph.D.   
   Rockefeller University, New York, NY   
   pbieniasz@rockefeller.edu   
      
   Supported by grants from the National Institutes of Health   
   (R37AI64003 and R01AI501111, to Dr. Bieniasz; R01AI78788, to Dr.   
   Hatziioannou; and P01-AI138398-S1 and 2U19AI111825, to Dr.   
   Nussenzweig). Dr. Gaebler’s work is supported by the Robert S.   
   Wennett Post-Doctoral Fellowship, the National Center for Advancing   
   Translational Sciences (National Institutes of Health Clinical and   
      
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