Pathogen entry into cells, host immune responses & vaccine design: structural biology, protein design, virology & immunology @HHMINEWS @UWBiochemistry
Nov 1 • 6 tweets • 2 min read
Excited to share our latest work elucidating the mechanisms of coronavirus entry into cells!
Led by @Dr_MattMcCallum on our side in collaboration with Huan Yan's lab (TaiKang Center for Life and Medical Sciences)
1/5nature.com/articles/s4158…
In 2019, we proposed w @coronalexington @axiong_x that coronavirus entry into cells involves a spike (S) molecular ratcheting mechanism & discovered that antibodies could functionally mimic the receptor by inducing these S conformational changes
How many times did coronaviruses evolve the ability to use ACE2 as receptor for infection? Find out by reading this @biorxivpreprint in collab with Huan Yan (Wuhan Univ)
Led by Ma CB, Liu C @YoungjunPark11 Tang J & Chen J
@HHMINEWS
@UWBiochemistry
1/9 biorxiv.org/content/10.110…
We previously described the unexpected discovery that MERS-related coronaviruses (MERSr-CoVs) discovered in African bats use ACE2 as receptor instead of the MERS-CoV receptor DPP4 (as described in this thread )
A few months ago, we asked if imprinting impacts immune responses to the recently updated XBB.1.5 spike (S) #COVID19 booster? The peer-reviewed version of our manuscript is now available
@HHMINEWS @UWBiochemistry
Are you wondering how the human coronavirus HKU1 recognizes the TMPRSS2 host receptor?
Find out in our @biorxivpreprint led by
@Dr_MattMcCallum @YoungjunPark11
@HHMINEWS @UWBiochemistry
1/26 biorxiv.org/content/10.110…
HKU1 was discovered in 2005 from a patient with pneumonia (it was circulating for ≥10 years) and is endemic in humans. HKU1 is an embecovirus, a subgenus for which the entry process into cells is less well understood than for most other betaCoVs such as #SARSCoV2
2/26
Dec 14, 2023 • 22 tweets • 7 min read
Can we design #COVID19 vaccines that are largely insensitive to viral evolution? Find out by reading our @biorxivpreprint preprint
Led by @0327jimin
@HHMINEWS @UWBiochemistry
1/22
biorxiv.org/content/10.110…
Coronavirus spike (S) glycoproteins comprise the S1 subunit, which mediates attachment to host receptor(s), and the S2 subunit (fusion machinery) that promotes fusion of the viral and host membranes to initiate infection
2/22
Dec 1, 2023 • 18 tweets • 5 min read
Is imprinting impacting immune responses to the recently updated XBB.1.5 spike (S) #COVID19 booster? Find out by reading our preprint or this thread!
Led by @aletortorici
@HHMINEWS @UWBiochemistry
1/18
biorxiv.org/content/10.110…
Immune imprinting - AKA original antigenic sin - describes how the first exposure to a virus shapes the immunological outcome of subsequent exposures to antigenically related strains.
2/18
Sep 14, 2023 • 23 tweets • 6 min read
How do bat-borne sarbecoviruses (i.e. SARS-CoV-1/2-like viruses) interact with host receptors and are we ready for a possible future pandemic?
Find out in this study led by @0327jimin & @Sam_K_Zepeda !
@HHMINEWS @UWBiochemistry
1/23
biorxiv.org/content/10.110…
Spillover of SARS-CoV-1 and #SARSCoV2 from Rinolophus bat origin led to the SARS epidemic and the #COVID19 pandemic. Reports of additional sarbecovirus spillovers & detection in Rhinolophus bats and other animals underscore their recurrent zoonotic threat to public health
2/23
Aug 21, 2023 • 19 tweets • 6 min read
Have you heard of the recently emerged Langya virus (LayV) which was detected in humans last year? Find out more by reading our @biorxivpreprint led by @pbpwang @Dr_MattMcCallum & Lianying Yan!
1/19
biorxiv.org/content/10.110…
LayV is a recently discovered henipavirus (HNV), isolated from febrile patients in China, harboring a genome distantly related to that of Nipah virus (NiV) and Hendra virus (HeV)
1/10
Here are a few thoughts on what distinguishes the cohorts you analyzed vs the ones we recently analyzed for which we found few de novo elicited memory B cells, as described here
1/ biorxiv.org/content/10.110…
Currently circulating #SARSCoV2 variants are evolving from the Omicron BA.2 and BA.5 lineages, through independent accumulation of amino acid mutations at shared receptor-binding domain (RBD) hot spots, underscoring the importance of antibody-mediated selective pressure.
2/
Dec 7, 2022 • 18 tweets • 8 min read
Can coronaviruses keep surprising us?
Yes - we joined forces with Xiangxi Wang (Chinese Acad of Sci, Beijing) & Huan Yan (Wuhan Univ) to show that close relatives of MERS-CoV found in bats use ACE2 as host cell receptor! @HHMINEWS @UWBiochemistry
1/18 nature.com/articles/s4158…
MERS-CoV (Middle-East respiratory syndrome coronavirus), is a pathogen that emerged in 2012 and caused several outbreaks in the Middle-East and South Korea with a 35% fatality rate
The peer-reviewed version of our manuscript describing the influence of the #SARSCoV2 spike glycoprotein conformation on vaccine- and infection-elicited antibody responses in humans is out!
The peer-reviewed version of our manuscript assessing human neutralizing antibodies against key #Omicron variant sublineages elicited by a comprehensive panel of vaccines is now out
science.org/doi/10.1126/sc…
The thread describing our @biorxivpreprint submission can be found here and we added a large amount of data during the reviewing process (cf. thread below).
biorxiv.org/content/10.110…
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
2/24
Mar 17, 2022 • 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.
biorxiv.org/content/10.110…
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!
2/13
Feb 9, 2022 • 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.
biorxiv.org/content/10.110…
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 characterized the structural basis of #SARSCoV2#OmicronVariant binding to the host ACE2 receptor and neutralization by the S309/sotrovimab clinical antibody therapeutic!
Led by @Dr_MattMcCallum & Nadine Czudnochowski Collab w Gyorgy Snell
1/8
biorxiv.org/content/10.110…
We show that the #OmicronVariant spike NTD antigenic supersite is structurally rearranged, relative to the Wuhan-Hu-1 NTD, explaining the loss of binding and neutralization by a panel of NTD-targeted monoclonal antibodies we recently evaluated (nature.com/articles/d4158…).
