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Article ; Online: Neuroinvasive Flavivirus Pathogenesis Is Restricted by Host Genetic Factors in Collaborative Cross Mice, Independently of

Jasperse, Brittany A / Mattocks, Melissa D / Noll, Kelsey E / Ferris, Martin T / Heise, Mark T / Lazear, Helen M

2023 Volume 97, Issue 7, Page(s) e0071523

Abstract: Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive diseases, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encephalitis virus ( ... ...

Abstract	Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive diseases, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encephalitis virus (JEV), POWV disease presentation is heterogeneous, and the factors influencing disease outcome are not fully understood. We used Collaborative Cross (CC) mice to assess the impact of host genetic factors on POWV pathogenesis. We infected a panel of
MeSH term(s)	Humans ; Mice ; Animals ; Flavivirus/genetics ; Collaborative Cross Mice ; Flavivirus Infections/genetics ; West Nile virus ; Encephalitis Viruses, Tick-Borne/physiology ; Encephalitis Virus, Japanese/genetics ; Encephalitis ; Disease Susceptibility ; Paralysis ; 2',5'-Oligoadenylate Synthetase/genetics
Chemical Substances	Oas1b protein, mouse (EC 2.7.7.-) ; 2',5'-Oligoadenylate Synthetase (EC 2.7.7.84)
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00715-23
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Article ; Online: Altered m

Gokhale, Nandan S / McIntyre, Alexa B R / Mattocks, Melissa D / Holley, Christopher L / Lazear, Helen M / Mason, Christopher E / Horner, Stacy M

Molecular cell

2019 Volume 77, Issue 3, Page(s) 542–555.e8

Abstract: The RNA modification ... ...

Abstract	The RNA modification N
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/genetics ; Cell Line ; Dengue/virology ; Dengue Virus/genetics ; Flaviviridae/genetics ; Flaviviridae Infections/genetics ; Hepacivirus/genetics ; Hepatitis C/virology ; Host-Pathogen Interactions/genetics ; Humans ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Virus Replication/genetics ; Zika Virus/genetics ; Zika Virus Infection/genetics
Chemical Substances	CIRBP protein, human ; RNA, Messenger ; RNA-Binding Proteins ; N-methyladenosine (CLE6G00625) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; RIO kinase 3, human (EC 2.7.11.1) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.11.007
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Article: Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.

Voss, William N / Mallory, Michael A / Byrne, Patrick O / Marchioni, Jeffrey M / Knudson, Sean A / Powers, John M / Leist, Sarah R / Dadonaite, Bernadeta / Townsend, Douglas R / Kain, Jessica / Huang, Yimin / Satterwhite, Ed / Castillo, Izabella N / Mattocks, Melissa / Paresi, Chelsea / Munt, Jennifer E / Scobey, Trevor / Seeger, Allison / Premkumar, Lakshmanane /

Bloom, Jesse D / Georgiou, George / McLellan, Jason S / Baric, Ralph S / Lavinder, Jason J / Ippolito, Gregory C

bioRxiv : the preprint server for biology

2024

Abstract: We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post- ... ...

Abstract	We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K Highlights: ▪ Infection and vaccination elicit unique IgG antibody profiles at the molecular level▪ Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)▪ Hybrid immunity maintains the imprint of first infection or first vaccination▪ Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth.
Language	English
Publishing date	2024-01-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.22.576742
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Article ; Online: Cryptic-site-specific antibodies to the SARS-CoV-2 receptor binding domain can retain functional binding affinity to spike variants.

Li, Kan / Huntwork, Richard H C / Horn, Gillian Q / Abraha, Milite / Hastie, Kathryn M / Li, Haoyang / Rayaprolu, Vamseedhar / Olmedillas, Eduardo / Feeney, Elizabeth / Cronin, Kenneth / Schendel, Sharon L / Heise, Mark / Bedinger, Daniel / Mattocks, Melissa D / Baric, Ralph S / Alam, S Munir / Ollmann Saphire, Erica / Tomaras, Georgia D / Dennison, S Moses

Journal of virology

2023 Volume 97, Issue 12, Page(s) e0107023

Abstract: Importance: Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is ... ...

Abstract	Importance: Multiple SARS-CoV-2 variants of concern have emerged and caused a significant number of infections and deaths worldwide. These variants of concern contain mutations that might significantly affect antigen-targeting by antibodies. It is therefore important to further understand how antibody binding and neutralization are affected by the mutations in SARS-CoV-2 variants. We highlighted how antibody epitope specificity can influence antibody binding to SARS-CoV-2 spike protein variants and neutralization of SARS-CoV-2 variants. We showed that weakened spike binding and neutralization of Beta (B.1.351) and Omicron (BA.1) variants compared to wildtype are not universal among the panel of antibodies and identified antibodies of a specific binding footprint exhibiting consistent enhancement of spike binding and retained neutralization to Beta variant. These data and analysis can inform how antigen-targeting by antibodies might evolve during a pandemic and prepare for potential future sarbecovirus outbreaks.
MeSH term(s)	Humans ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/metabolism ; Antibodies, Viral/chemistry ; Antibodies, Viral/immunology ; Antibodies, Viral/metabolism ; COVID-19 ; SARS-CoV-2/genetics ; Severe acute respiratory syndrome-related coronavirus ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01070-23
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Host range, transmissibility and antigenicity of a pangolin coronavirus.

Hou, Yixuan J / Chiba, Shiho / Leist, Sarah R / Meganck, Rita M / Martinez, David R / Schäfer, Alexandra / Catanzaro, Nicholas J / Sontake, Vishwaraj / West, Ande / Edwards, Catlin E / Yount, Boyd / Lee, Rhianna E / Gallant, Samuel C / Zost, Seth J / Powers, John / Adams, Lily / Kong, Edgar F / Mattocks, Melissa / Tata, Aleksandra /

Randell, Scott H / Tata, Purushothama R / Halfmann, Peter / Crowe, James E / Kawaoka, Yoshihiro / Baric, Ralph S

Nature microbiology

2023 Volume 8, Issue 10, Page(s) 1820–1833

Abstract: The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. ...

Abstract	The pathogenic and cross-species transmission potential of SARS-CoV-2-related coronaviruses (CoVs) remain poorly characterized. Here we recovered a wild-type pangolin (Pg) CoV GD strain including derivatives encoding reporter genes using reverse genetics. In primary human cells, PgCoV replicated efficiently but with reduced fitness and showed less efficient transmission via airborne route compared with SARS-CoV-2 in hamsters. PgCoV was potently inhibited by US Food and Drug Administration approved drugs, and neutralized by COVID-19 patient sera and SARS-CoV-2 therapeutic antibodies in vitro. A pan-Sarbecovirus antibody and SARS-CoV-2 S2P recombinant protein vaccine protected BALB/c mice from PgCoV infection. In K18-hACE2 mice, PgCoV infection caused severe clinical disease, but mice were protected by a SARS-CoV-2 human antibody. Efficient PgCoV replication in primary human cells and hACE2 mice, coupled with a capacity for airborne spread, highlights an emergence potential. However, low competitive fitness, pre-immune humans and the benefit of COVID-19 countermeasures should impede its ability to spread globally in human populations.
MeSH term(s)	Cricetinae ; Humans ; Animals ; Mice ; Host Specificity ; Pangolins ; SARS-CoV-2/genetics ; COVID-19/prevention & control ; Severe acute respiratory syndrome-related coronavirus ; Antibodies, Viral ; COVID-19 Vaccines ; Mice, Inbred BALB C
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2023-09-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01476-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Zika virus infection in Collaborative Cross mice

Mattocks, Melissa D. / Plante, Kenneth S. / Fritch, Ethan J. / Baric, Ralph S. / Ferris, Martin T. / Heise, Mark T. / Lazear, Helen M.

bioRxiv

Abstract: The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV infection during pregnancy can result in birth defects, revealed a need for small animal models to study ZIKV pathogenic mechanisms and evaluate candidate vaccines ... ...

Abstract	The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV infection during pregnancy can result in birth defects, revealed a need for small animal models to study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies have used mice with impaired interferon signaling (e.g. Ifnar1−/− or treatment with IFNAR1-blocking antibodies). However, using mice with severe defects in innate antiviral signaling confounds studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a valuable system for developing new mouse pathogenesis models for viral infections that are not well modeled in conventional laboratory mouse lines. To test whether CC mice could provide an immune-competent model for ZIKV pathogenesis, we infected CC lines with ZIKV and assessed weight loss, viremia, and production of neutralizing antibodies. We tested 21 CC lines (CC001, CC002, CC003, CC004, CC005, CC006, CC011, CC012, CC013, CC019, CC024, CC028, CC040, CC041, CC042, CC046, CC051, CC059, CC061, CC068, and CC072, 13 of which have non-functional alleles of the flavivirus restriction factor Oas1b) and 3 ZIKV strains (MR766, H/PF/2013, and a mouse-adapted variant of Dakar 41525). ZIKV infection did not induce weight loss compared to mock-infected controls and accordingly only low levels of viral RNA were detected in serum. Only a subset of mice developed neutralizing antibodies to ZIKV, likely due to overall low levels of infection and viremia. Our results are consistent with other studies demonstrating poor ZIKV infection in interferon-intact mice and suggest that the tested CC lines do not include polymorphic host genes that greatly increase susceptibility to ZIKV infection.
Keywords	covid19
Publisher	BioRxiv; MedRxiv
Document type	Article ; Online
DOI	10.1101/695510
Database	COVID19

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Article ; Online: Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination

Voss, William N. / Mallory, Michael A. / Byrne, Patrick O. / Marchioni, Jeffrey M. / Knudson, Sean A. / Powers, John M. / Leist, Sarah R. / Dadonaite, Bernadeta / Townsend, Douglas R. / Kain, Jessica / Huang, Yimin / Satterwhite, Ed / Castillo, Izabella N. / Mattocks, Melissa / Paresi, Chelsea / Munt, Jennifer E. / Scobey, Trevor / Seeger, Allison / Premkumar, Lakshmanane /

Bloom, Jesse D. / Georgiou, George / McLellan, Jason S. / Baric, Ralph S. / Lavinder, Jason J. / Ippolito, Gregory C.

bioRxiv

Abstract	We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K<sub>D</sub> < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC<sub>50</sub> ~0.1–1.75 nM) and provided robust protection in vivo. Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization.
Keywords	covid19
Language	English
Publishing date	2024-01-23
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.22.576742
Database	COVID19

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Article ; Online: Durability of Heterologous and Homologous COVID-19 Vaccine Boosts.

Tan, C Sabrina / Collier, Ai-Ris Y / Yu, Jingyou / Liu, Jinyan / Chandrashekar, Abishek / McMahan, Katherine / Jacob-Dolan, Catherine / He, Xuan / Roy, Vicky / Hauser, Blake M / Munt, Jennifer E / Mallory, Michael L / Mattocks, Melissa / Powers, John M / Meganck, Rita M / Rowe, Marjorie / Hemond, Rachel / Bondzie, Esther A / Jaegle, Kate H /

Baric, Ralph S / Schmidt, Aaron G / Alter, Galit / Le Gars, Mathieu / Sadoff, Jerald / Barouch, Dan H

JAMA network open

2022 Volume 5, Issue 8, Page(s) e2226335

Abstract: Importance: Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting.: Objective: To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens ... ...

Abstract	Importance: Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting. Objective: To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2. Design, setting, and participants: In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022. Exposures: Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2. Main outcomes and measures: Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays. Results: Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16. Conclusions and relevance: Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.
MeSH term(s)	Ad26COVS1 ; Adult ; Antibodies, Neutralizing ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Cohort Studies ; Female ; Humans ; Male ; SARS-CoV-2 ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; Antibodies, Neutralizing ; COVID-19 Vaccines ; Vaccines, Synthetic ; mRNA Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2022.26335
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Article ; Online: A tetravalent alphavirus-vector based dengue vaccine provides effective immunity in an early life mouse model.

Khalil, Syed Muaz / Tonkin, Daniel R / Mattocks, Melissa D / Snead, Andrew T / Johnston, Robert E / White, Laura J

Vaccine

2014 Volume 32, Issue 32, Page(s) 4068–4074

Abstract: Dengue viruses (DENV1-4) cause 390 million clinical infections every year, several hundred thousand of which progress to severe hemorrhagic and shock syndromes. Preexisting immunity resulting from a previous DENV infection is the major risk factor for ... ...

Abstract	Dengue viruses (DENV1-4) cause 390 million clinical infections every year, several hundred thousand of which progress to severe hemorrhagic and shock syndromes. Preexisting immunity resulting from a previous DENV infection is the major risk factor for severe dengue during secondary heterologous infections. During primary infections in infants, maternal antibodies pose an analogous risk. At the same time, maternal antibodies are likely to prevent induction of endogenous anti-DENV antibodies in response to current live, attenuated virus (LAV) vaccine candidates. Any effective early life dengue vaccine has to overcome maternal antibody interference (leading to ineffective vaccination) and poor induction of antibody responses (increasing the risk of severe dengue disease upon primary infection). In a previous study, we demonstrated that a non-propagating Venezuelan equine encephalitis virus replicon expression vector (VRP), expressing the ectodomain of DENV E protein (E85), overcomes maternal interference in a BALB/c mouse model. We report here that a single immunization with a tetravalent VRP vaccine induced NAb and T-cell responses to each serotype at a level equivalent to the monovalent vaccine components, suggesting that this vaccine modality can overcome serotype interference. Furthermore, neonatal immunization was durable and could be boosted later in life to further increase NAb and T-cell responses. Although the neonatal immune response was lower in magnitude than responses in adult BALB/c mice, we demonstrate that VRP vaccines generated protective immunity from a lethal challenge after a single neonatal immunization. In summary, VRP vaccines expressing DENV antigens were immunogenic and protective in neonates, and hence are promising candidates for safe and effective vaccination in early life.
MeSH term(s)	Animals ; Animals, Newborn ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Dengue/prevention & control ; Dengue Vaccines/immunology ; Encephalitis Virus, Venezuelan Equine ; Female ; Mice, Inbred BALB C ; Neutralization Tests ; Pregnancy ; T-Lymphocytes/immunology ; Viral Envelope Proteins/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Dengue Vaccines ; E protein, Dengue virus type 3 ; Viral Envelope Proteins
Language	English
Publishing date	2014-05-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2014.05.053
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Article: Engineered Immunogens to Elicit Antibodies Against Conserved Coronavirus Epitopes.

Kapingidza, Brenda / Marston, Daniel J / Harris, Caitlin / Wrapp, Daniel / Winters, Kaitlyn / Mielke, Dieter / Xiaozhi, Lu / Yin, Qi / Foulger, Andrew / Parks, Rob / Barr, Maggie / Newman, Amanda / Schäfer, Alexandra / Eaton, Amanda / Flores, Justine Mae / Harner, Austin / Cantazaro, Nicholas J / Mallory, Michael L / Mattocks, Melissa D /

bioRxiv : the preprint server for biology

2023

Abstract: Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues ... ...

Abstract	Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employed computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant RBD. These engineered proteins bound with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interacted with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicited sera with broad betacoronavirus reactivity and protected as "boosts" against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
Language	English
Publishing date	2023-09-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.27.530277
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