We assessed plasma neutralizing activity from humans previously infected in 2020 (WA-1-like) and then vaxed 2x or 3x, or vaxed before Delta or #Omicron BA.1 breakthrough infection or vaxed-'only' 3x
Mar 17 • 13 tweets • 7 min read
Excited to share our latest serological data evaluating plasma neutralizing antibody responses and immune evasion associated with the constellation of spike mutations present in the #Omicron BA.1 and BA.2 variants.
We compared side-by-side the plasma neutralizing activity elicited in humans by seven #COVID19 vaccines (Moderna, Pfizer, Novavax, Janssen, AstraZeneca, Sputnik V and Sinopharm) or SARS-CoV-2 Washington-1 infection. We cover mRNA, Ad-vectored and protein subunit vaccines!
Feb 9 • 6 tweets • 4 min read
Throughout the pandemic, we have been puzzled with inconsistencies in the observed breadth of polyclonal serum neutralizing antibodies against #SARSCoV2 variants in mice vs humans or non-human primates.
Serum neutralizing antibodies titers represent the current best correlate of protection against #SARSCoV2 used to evaluate and compare vaccine-elicited immunity in animal models and humans.
Delighted to share our study of the #SARSCoV2 E406W spike mutant describing how a single amino acid mutation mediates escape from the REGN10987/REGN10933 antibody cocktail despite residing outside their epitopes
The peer-reviewed version of our manuscript describing the structures of the #SARS_CoV_2#OmicronVariant spike bound to the clinical S309 antibody (sotrovimab parent) and receptor-binding domain bound to ACE2 (and S309/S304) is now available here.
We compared antibody responses elicited by 6 #CovidVaccine distributed globally: Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, AstraZeneca AZD1222, Gamaleya Sputnik V and Sinopharm BBIBP-CorV, after 2 doses, Janssen Ad26.COV2.S after 1 dose, and human convalescent plasma
1/8#SARSCoV2#Omicron harbors a staggering 37 amino acid mutations in the spike with 15 of them in the receptor-binding domain (RBD), which is the main target of neutralizing antibodies. The number and positions of these mutations is concerning for tropism & immune evasion.
Dec 10, 2021 • 15 tweets • 8 min read
Are you wondering what antibody responses are like in #SARSCoV2 Delta breakthrough patients?
We followed 4 cohorts longitudinally for up to 6 months:
-Delta breakthrough (vaccinated then infected)
-subjects infected and then vaccinated (2x and 3x)
-vaccinated-only (2x and 3x)
Have you heard of the recently discovered 8th human-infecting #coronavirus designated CCoV-HuPn-2018?
We reveal the architecture of its spike (ie infection machinery), receptor usage and antigenic properties!
CCoV-HuPn-2018 is a canine-feline recombinant alpha-#coronavirus isolated from the respiratory swab of a child hospitalized with pneumonia, indicating that more coronaviruses are spilling over to humans than previously appreciated.
S2K146 binds and broadly neutralizes several SARS-CoV-1-like and SARS-CoV-2-like viruses (clades 1a/1b). It inhibits BtKY72 (clade 3) K493Y/T498W S pseudovirus, as we previously showed that these 2 mutations enable this bat virus to use hACE2.
Sharing our latest preprint on #SARSCoV2 B.1.617.2 (delta), B.1.617.2+ (delta+) and B.1.617.1 (kappa) variants led by @Dr_MattMcCallum
We show that vaccine-elicited neutralizing activity is reduced against delta and kappa and even more against delta+ relative to the vaccine-matched pseudovirus. Delta+ reduces neutralization ~ to B.1.351 (beta) which has the greatest magnitude of immune evasion thus far.
The #SARSCoV2 CAL20.C (B.1.427/B.1.429) variant comprises 3 spike mutations: S13I, W152C & L452R reducing plasma neutralizing activity by ~3x and ~5x for vaccine- and infection-elicited antibodies (Abs), compared to the 'ancestral' virus.
We found that NTD-specific mAbs account for 6-20% of mAbs cloned from memory B cells in #COVID19 patients and that the most potent of them neutralize #SARSCoV2 as efficiently as ultrapotent RBD-specific mAbs and trigger Fc-mediated effector functions effectively.
Dec 30, 2020 • 6 tweets • 4 min read
We discovered a neutralizing mouse monoclonal antibody (B6) targeting the coronavirus spike fusion machinery (S2 subunit) in collaboration with @McGuire_Lab
We identified by cryoEM that B6 recognizes the spike stem helix and cross-reacts with at least 8 distinct coronavirus spikes including those of the three highly pathogenic (#SARSCoV2, SARS-CoV and MERS-CoV) and the two endemic (OC43 and HKU1) human β-coronaviruses.
Oct 30, 2020 • 6 tweets • 4 min read
The peer-reviewed version of our article describing the design and evaluation of a multivalent #SARSCoV2 receptor-binding domain #COVID19 vaccine is out!
Based on our previous studies of the immune response to coronavirus infections, we identified that the receptor-binding domain is immunodominant and accounts for most of the neutralizing activity in convalescent plasma/sera.