SARS-CoV-2 spike subunit conformation determines plasma-neutralizing activity triggered by COVID-19 vaccines and natural infection UW SARSCoV2 COVID19 Vaccination NaturalInfection Vaccine
By Neha MathurNov 14 2022Reviewed by Aimee Molineux In a recent study published in Science Immunology, researchers evaluated the effect of the severe acute respiratory syndrome coronavirus 2 spike glycoprotein conformation on S-directed neutralizing antibodies .
The team retrieved serum samples from individuals not previously exposed to SARS-CoV-2 but recipients of a primary vaccination series of any of the following vaccines: mRNA-1273, BNT162b2, NVX-CoV2373, and Ad26.COV2.S, AZD1222, Sputnik V, or BBIBP-CorV. They benchmarked these samples against COVID-19 convalescent plasma obtained from people infected with the Wuhan-Hu1 strain before or in January 2021.
The recipients of a two-dose regimen of NVX-CoV2373, Ad26.COV2.S, AZD1222, Sputnik V, and BBIBP-CorV displayed intermediate prefusion S binding with GMTs of 4.8, 5.3, 6.3, 5.0, and 5.2, respectively. Intriguingly, the trend did not change when the researchers computed S binding titers using the S1 subunit, the NTD, or the RBD as ELISA antigens.
The explanation for such observations lies hidden in the metastable nature of the S trimer. The S trimer is inherently prone to shedding the S1 subunit and refolding to form post-fusion trimers; thus, the absence of prefusion-stabilizing S mutations in the AZD1222 vaccine explains why it elicited slightly lower S/S2 binding ratios relative to BNT162b2 and Ad26.COV2.S.
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