Kaitlin R. Sprouse
A5029869163- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- Viral Infections and Immunology Research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Complement system in diseases
- Long-Term Effects of COVID-19
- Bacillus and Francisella bacterial research
- Virus-based gene therapy research
- Animal Disease Management and Epidemiology
- Immunodeficiency and Autoimmune Disorders
- Virology and Viral Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Immune responses and vaccinations
- Bacteriophages and microbial interactions
- Advanced biosensing and bioanalysis techniques
- interferon and immune responses
University of Washington
2021-2024
Howard Hughes Medical Institute
2024
A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I the signal peptide, W152C N-terminal domain (NTD), and L452R receptor-binding (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or convalescent exhibited neutralizing titers that were reduced 2- to 3.5-fold against B.1.427/B.1.429 relative wild-type pseudoviruses. The mutation activity 14 34...
How the Delta variant evades defenses In course of COVID-19 epidemic, variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, some which evade immunity or increase transmission. late 2020, and Kappa were detected, became globally dominant by June 2021. McCallum et al . show that vaccine-elicited serum-neutralizing activity is reduced against these variants. Based on biochemistry structural studies, authors mutations in domain binds ACE2 receptor abrogate...
Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that induce serum-binding -neutralizing are markedly more potent, durable, resilient spike mutations observed variants than subjects who received only 2 doses vaccine. However, show cases, were after infection, three times have serum-neutralizing...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters elicit plasma-neutralizing against BA.1, BA.2, BA.2.12.1, and BA.4/5, breakthrough infections, but not vaccination alone, induce neutralizing the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells plasma of cases...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 BA.4 BA.5 increasing in prevalence worldwide. We show that large number sublineage spike mutations leads to enhanced angiotensin-converting enzyme (ACE2) binding, reduced fusogenicity, dampening plasma neutralizing activity elicited by infection or seven clinical vaccines relative ancestral virus....
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation characterization of a human monoclonal antibody, designated S2K146, that neutralizes viruses belonging SARS-CoV- SARS-CoV-2-related clades which use ACE2 as an entry receptor. Structural functional studies show most virus residues directly bind S2K146 are also involved in binding ACE2. This allows...
Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding...
Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies engineering strategies. We show here containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of the
The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. molecular basis of binding TMPRSS2 determinants receptor tropism remain elusive. We designed an active construct enabling high-yield recombinant production in cells this key therapeutic target. determined a cryo-electron microscopy structure the RBD bound TMPRSS2, providing blueprint interactions supporting viral entry explaining...
The SARS-CoV-2 Omicron variant of concern comprises three sublineages designated BA.1, BA.2, and BA.3, with BA.2 steadily replacing the globally dominant BA.1. We show that large number BA.1 spike mutations severely dampen plasma neutralizing activity elicited by infection or seven clinical vaccines, cross-neutralization being consistently more potent than independent vaccine platform doses. Although mRNA vaccines induced greatest magnitude activity, administration a booster based on...
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters result potent plasma neutralizing activity against BA.1 BA.2 breakthrough infections, but not vaccination-only, induce the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells of cases cross-react Wuhan-Hu-1, receptor-binding domains whereas...
The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development countermeasures provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive...
Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots 1 . Their impact on viral infection, transmission, and efficacy of vaccines therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. XBB.1 bind ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures the BQ.1.1 RBDs bound to human S309 Fab (sotrovimab parent) explain altered recognition...
The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. molecular basis of binding TMPRSS2 determinants receptor tropism remain elusive. Here, we designed an active construct enabling high-yield recombinant production in cells this key therapeutic target. We determined a cryo-electron microscopy structure the RBD bound providing blueprint interactions supporting viral entry explaining...
Abstract Evolution of SARS-CoV-2 alters the antigenicity immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining efficacy vaccines antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing responses on highly conserved but metastable S 2 subunit, which folds as spring-loaded fusion machinery. We describe strategy for prefusion-stabilization high yield recombinant production trimers with native structure antigenicity. demonstrate that...
Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012 and causes human infections endemic regions. Vaccines therapeutics development against MERS-CoV focus on the spike (S) glycoprotein to prevent viral entry into target cells. These efforts are limited by a poor understanding of antibody responses elicited infection. Here, we analyze S-directed plasma collected from MERS-CoV-infected individuals. We observe that binding neutralizing antibodies peak 1–6 weeks after...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing sufficiently potent clinical development and retain activity despite remain elusive. We identified human mAb, designated VIR-7229, which targets the receptor-binding motif (RBM) with unprecedented cross-reactivity all sarbecovirus clades,...
Worldwide SARS-CoV-2 transmission leads to the recurrent emergence of variants, such as recently described B.1.617.1 (kappa), B.1.617.2 (delta) and B.1.617.2+ (delta+). The variant concern is causing a new wave infections in many countries, mostly affecting unvaccinated individuals, has become globally dominant. We show that these variants dampen vitro potency vaccine-elicited serum neutralizing antibodies provide structural framework for describing impact individual mutations on immune...
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are receptor-binding domain (RBD), thereby raising concerns about effectiveness available vaccines and antibody therapeutics. Here, we show that RBD binds to human ACE2 with enhanced affinity relative Wuhan-Hu-1 acquires binding mouse ACE2. Severe reductions plasma neutralizing activity were observed against compared ancestral pseudovirus for vaccinated convalescent...
Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety efficacy. Yet the rules for how immune responses specific to affect immunogenicity displayed antigens not been established. Here we define relationships between anti-scaffold antigen-specific antibody elicited by protein immunogens. We report that dampening physical masking does enhance responses. In a series immunogens all use same scaffold but...
Abstract We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The is switchable, caged luciferase–receptor-binding domain (RBD) construct detects serum-antibody interference with the binding virus RBD to angiotensin-converting enzyme (ACE-2) as proxy neutralization. Our approach does not require target modification can better...
Continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is eroding antibody responses elicited by prior vaccination and infection. The SARS-CoV-2 receptor-binding domain (RBD) E406W mutation abrogates neutralization mediated the REGEN-COV therapeutic monoclonal (mAb) COVID-19 cocktail AZD1061 (COV2-2130) mAb. Here, we show that this remodels site allosterically, thereby altering epitopes recognized these three mAbs vaccine-elicited neutralizing antibodies while...