At 5 months after vaccination, the neutralization potency was 5823 times lower for PMS20 and 2717 times lower for omicron (Fig. 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 6047 and 3727 times lower for PMS20 than for Wuhan-hu-1, respectively, and 5851 and 3223 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 3424 times lower for PMS20 and 4323 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 [PfizerCBioNTech] or mRNA-1273 [Moderna]) 1.3 months before sampling, the NT50 values were 18724 times lower for PMS20 and 12766 times lower for omicron than for Wuhan-hu-1 (Fig. S3A). At 5 months after vaccination, the neutralization potency was 5823 times lower for PMS20 and 2717 times lower for omicron (Fig. S3B). Many plasma specimens from recipients of the single-dose Ad26.COV2.S vaccine (Johnson & JohnsonCJanssen), 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 Tonapofylline Covid-19 or administration of a third dose of an mRNA vaccine to vaccinated persons at least 6 months Rabbit Polyclonal to TSC22D1 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 Tonapofylline 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, Tonapofylline 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 Tonapofylline 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). Open in a separate window Figure 1 Wuhan-hu-1, PMS20, and Omicron Plasma Neutralizing Titers.Panel A shows the trajectories of NT50 values against Wuhan-hu-1, polymutant spike protein (PMS20), and omicron pseudotypes in previously unvaccinated persons who had recovered from Covid-19, measured approximately 1 month (mean SD, 4112 days) and 6 months (19412 days) after infection and then at approximately 1 year (36015 days) after infection, which corresponded to 4121 days after vaccination (plus vaccine) (see Table S2). Panel B shows the trajectories of NT50 values against Wuhan-hu-1, PMS20, and omicron pseudotypes in persons who had received an mRNA vaccine, measured 1 month (4219 days) and 5 months (16533 days) after the second dose of an mRNA vaccine and at 3018 days after the third dose (boost) that was administered at least 6 months after the second dose. 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-1Cbased vaccine immunogens, will provide additional protection against infection with the omicron variant and subsequent disease. Supplementary Appendix Click here for additional data file.(1.2M, pdf) Disclosure Forms Click here for additional data file.(339K, pdf) Notes This letter was published on December 30, 2021, at NEJM.org. Footnotes Supported by grants from the (R37AI64003 and R01AI501111, to Dr. Bieniasz; R01AI78788, to Dr. Hatziioannou; and P01-AI138398-S1 and 2U19AI111825, to Dr. Nussenzweig). Dr. Gaeblers work is supported by the Robert S. Wennett Post-Doctoral Fellowship, the (Clinical and Translational Science Award program, grant UL1 TR001866), and the ShapiroCSilverberg Fund for the Advancement of Translational Research. Drs. Bieniasz and Nussenzweig are Investigators. Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org..
