Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
Laser vaporization experiments with graphite in a supersonic cluster beam apparatus indicate that the smallest fullerene to form in substantial abundance is C(28). Although ab initio quantum chemical calculations predict that this cluster will favor a tetrahedral cage structure, it is electronically open shell. Further calculations reveal that C(28) in this structure should behave as a sort of hollow superatom with an effective valence of 4. This tetravalence should be exhibited toward chemical bonding both on the outside and on the inside of the cage. Thus, stable closed-shell derivatives of C(28) with large highest occupied molecular orbital-lowest unoccupied molecular orbital gaps should be attainable either by reacting at the four tetrahedral vertices on the outside of the C(28) cage to make, for example, C(28)H(4), or by trapping a tetravalent atom inside the cage to make endothedral fullerenes such as Ti@C(28). An example of this second, inside route to C(28) stabilization is reported here: the laser and carbon-arc production of U@C(28).
Buckminsterfullerene, c60, was prepared in gram quantities by contact-arc vaporization of a graphite rod in a 100-Torr atinospherc of helium. followed by extraction of the resultant graphitic soot with toluene. The dominance of C , in this extract was verified by mass, FTIR. and NMR spectroscopy. The molecule was successfully hydrogenated to C6,H,, via a Birch reduction and dehydrogenated back to bare c 6 0 by treatment with DDQ reagent. Cyclic voltammetry of C60 in methylene chloride rcvcaled highly reversible formation of at least two stable anionic forms of c 6 0 in solution. A broad new class of thcsc fulleride and fulleronium ions is anticipated, both with the internal cavity empty and with any one of a large number of elcmcnts inside, thus providing a means of fine-tuning the chemical, optical, and redox properties.
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