SARS-CoV-2 501Y.V2 (B.1.351), a novel lineage of coronavirus causing COVID-19, contains substitutions in two immunodominant domains of the spike protein. Here, we show that pseudovirus expressing 501Y.V2 spike protein completely escapes three classes of therapeutically relevant antibodies. This pseudovirus also exhibits substantial to complete escape from neutralization, but not binding, by convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and foreshadows reduced efficacy of spike-based vaccines. Individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), develop neutralizing antibodies that can persist for months 1,2. Neutralizing antibodies are considered the primary correlate of protection from infection and are being pursued as therapeutics 3,4. Interim analyses with monoclonal neutralizing antibodies have shown success, facilitating their authorization for emergency use 5,6. The SARS-CoV-2 receptor binding domain (RBD) exists in either an 'up' (receptor-accessible) or 'down' (receptor-shielded) conformation. RBD is the dominant neutralization target for this and other human coronaviruses 7,8. These antibodies can be broadly divided into four main classes, of which two overlap with the angiotensin converting enzyme 2 (ACE2) receptor binding site (Fig. 1a and Supplementary Fig. 1a) 9. Class 1 antibodies are most frequently elicited in SARS-CoV-2 infection and include a public antibody response to an epitope only accessible in the RBD 'up' conformation 10. Class 2 antibodies use more diverse VH-genes and bind to RBD 'up' and RBD 'down' conformations of spike. After RBD, the N-terminal domain (NTD) of spike is the next most frequently targeted by neutralizing antibodies, most of which target a single immunodominant site 11. We, and others, recently described a new SARS-CoV-2 lineage in South Africa, defined as Nextstrain clade 20H/501Y.V2 (PANGOLin lineage B.1.351) 12. This lineage is defined by nine

SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

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BackgroundSerotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.MethodsColonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.ResultsGBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P<0.0001). Serotype III was the most common invasive serotype in newborns less than 7 days (57.7%) and in infants 7 to 90 days of age (84.3%; P<0.001). Relative to serotype III, other serotypes showed reduced invasive potential: Ia (0.49; 95%CI 0.31–0.77), II (0.30; 95%CI 0.13–0.67) and V (0.38; 95%CI 0.17–0.83).ConclusionIn South Africa, an anti-GBS vaccine including serotypes Ia, Ib and III has the potential of preventing 74.1%, 85.4% and 98.2% of GBS associated with maternal vaginal-colonization, invasive disease in neonates less than 7 days and invasive disease in infants between 7–90 days of age, respectively.