Authors: Khan K, Karim F, Cele S, Reedoy K, San EJ, Lustig G, Tegally H, Rosenberg Y, Bernstein M, Jule Z, Ganga Y, Ngcobo N, Mazibuko M, Mthabela N, Mhlane Z, Mbatha N, Miya Y, Giandhari J, Ramphal Y, Naidoo T, Sivro A, Samsunder N, Kharsany A, Amoako D, Bhiman J, Manickchund N, Karim Q, Magula N, Abdool Karim SS, Gray G, Hanekom W, von Gottberg A, Milo R, Gosnell B, Lessells R, Moore P, de Olveira T, Moosa M-Y S, Sigal A
The extent to which Omicron infection, with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. We measured SARS-CoV-2 variant neutralization capacity in 39 Omicron sub-lineage BA.1 infected individuals in South Africa starting at a median of 6 (IQR 3-9) days post-symptoms onset and continuing until a last follow-up sample a median of 23 (IQR 19-27) days post-symptoms to allow BA.1 elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer-BNT162b2 or J&J-Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean titer (GMT) FRNT50 of 42 at enrollment to 575 at the last follow-up time-point (13.6-fold) in vaccinated and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1091 (5.7-fold) in vaccinated and 28 to 91 (3.0-fold) in unvaccinated participants. At the last time-point, unvaccinated BA.1 infected individuals had 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization, and 4.8-fold lower Omicron sub-lineage BA.2 neutralization relative to vaccinated, with low absolute levels of neutralization for the non-BA.1 viruses. These results indicate that vaccination combined with Omicron/BA.1 infection hybrid immunity should be protective against Delta and other variants. In contrast, infection with Omicron/BA.1 alone offers limited cross-protection despite moderate enhancement.