Nanocell COVID-19 vaccine triggers a novel immune response pathway producing high-affinity antibodies which neutralize all variants of concern

Most current anti-viral vaccines elicit a humoral and cellular immune response the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several V...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in immunology Vol. 13; p. 1038562
Main Authors Gao, Steven Y, Amaro-Mugridge, Nancy B, Madrid-Weiss, Jocelyn, Petkovic, Nikolina, Vanegas, Natasha, Visvanathan, Kumar, Williams, Bryan R G, MacDiarmid, Jennifer A, Brahmbhatt, Himanshu
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 27.01.2023
Subjects
Online AccessGet full text

Cover

Loading…
Abstract Most current anti-viral vaccines elicit a humoral and cellular immune response the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several Variants of Concern (VOC) and the rapid waning of memory B cell response requiring vaccine reformulation to cover dominant VOC S-proteins and multiple boosters. Here we show for the first time in mice and humans, that a bacterially derived, non-living, nanocell (EDV; EnGeneIC Dream Vector) packaged with plasmid expressed SARS-CoV-2 S-protein and α-galactosyl ceramide adjuvant (EDV-COVID-αGC), stimulates an alternate pathway due to dendritic cells (DC) displaying both S-polypeptides and αGC thereby recruiting and activating iNKT cells with release of IFNγ. This triggers DC activation/maturation, activation of follicular helper T cells (T ), cognate help to B cells with secretion of a cytokine milieu promoting B cell maturation, somatic hypermutation in germinal centers to result in high affinity antibodies. Surrogate virus neutralization tests show 90-100% neutralization of ancestral and early VOC in mice and human trial volunteers. EDV-COVID-αGC as a third dose booster neutralized Omicron BA. 4/5. Serum and PBMC analyses reveal long lasting S-specific memory B and T cells. In contrast, control EDVs lacking αGC, did not engage the iNKT/DC pathway resulting in antibody responses unable to neutralize all VOCs and had a reduced B cell memory. The vaccine is lyophilized, stored and transported at room temperature with a shelf-life of over a year.
AbstractList Most current anti-viral vaccines elicit a humoral and cellular immune response via the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several Variants of Concern (VOC) and the rapid waning of memory B cell response requiring vaccine reformulation to cover dominant VOC S-proteins and multiple boosters. Here we show for the first time in mice and humans, that a bacterially derived, non-living, nanocell (EDV; EnGeneIC Dream Vector) packaged with plasmid expressed SARS-CoV-2 S-protein and α-galactosyl ceramide adjuvant (EDV-COVID-αGC), stimulates an alternate pathway due to dendritic cells (DC) displaying both S-polypeptides and αGC thereby recruiting and activating iNKT cells with release of IFNγ. This triggers DC activation/maturation, activation of follicular helper T cells (T FH ), cognate help to B cells with secretion of a cytokine milieu promoting B cell maturation, somatic hypermutation in germinal centers to result in high affinity antibodies. Surrogate virus neutralization tests show 90-100% neutralization of ancestral and early VOC in mice and human trial volunteers. EDV-COVID-αGC as a third dose booster neutralized Omicron BA. 4/5. Serum and PBMC analyses reveal long lasting S-specific memory B and T cells. In contrast, control EDVs lacking αGC, did not engage the iNKT/DC pathway resulting in antibody responses unable to neutralize all VOCs and had a reduced B cell memory. The vaccine is lyophilized, stored and transported at room temperature with a shelf-life of over a year.
Most current anti-viral vaccines elicit a humoral and cellular immune response the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several Variants of Concern (VOC) and the rapid waning of memory B cell response requiring vaccine reformulation to cover dominant VOC S-proteins and multiple boosters. Here we show for the first time in mice and humans, that a bacterially derived, non-living, nanocell (EDV; EnGeneIC Dream Vector) packaged with plasmid expressed SARS-CoV-2 S-protein and α-galactosyl ceramide adjuvant (EDV-COVID-αGC), stimulates an alternate pathway due to dendritic cells (DC) displaying both S-polypeptides and αGC thereby recruiting and activating iNKT cells with release of IFNγ. This triggers DC activation/maturation, activation of follicular helper T cells (T ), cognate help to B cells with secretion of a cytokine milieu promoting B cell maturation, somatic hypermutation in germinal centers to result in high affinity antibodies. Surrogate virus neutralization tests show 90-100% neutralization of ancestral and early VOC in mice and human trial volunteers. EDV-COVID-αGC as a third dose booster neutralized Omicron BA. 4/5. Serum and PBMC analyses reveal long lasting S-specific memory B and T cells. In contrast, control EDVs lacking αGC, did not engage the iNKT/DC pathway resulting in antibody responses unable to neutralize all VOCs and had a reduced B cell memory. The vaccine is lyophilized, stored and transported at room temperature with a shelf-life of over a year.
Most current anti-viral vaccines elicit a humoral and cellular immune response via the pathway of phagocytic cell mediated viral antigen presentation to B and T cell surface receptors. However, this pathway results in reduced ability to neutralize S-protein Receptor Binding Domains (RBDs) from several Variants of Concern (VOC) and the rapid waning of memory B cell response requiring vaccine reformulation to cover dominant VOC S-proteins and multiple boosters. Here we show for the first time in mice and humans, that a bacterially derived, non-living, nanocell (EDV; EnGeneIC Dream Vector) packaged with plasmid expressed SARS-CoV-2 S-protein and α-galactosyl ceramide adjuvant (EDV-COVID-αGC), stimulates an alternate pathway due to dendritic cells (DC) displaying both S-polypeptides and αGC thereby recruiting and activating iNKT cells with release of IFNγ. This triggers DC activation/maturation, activation of follicular helper T cells (TFH), cognate help to B cells with secretion of a cytokine milieu promoting B cell maturation, somatic hypermutation in germinal centers to result in high affinity antibodies. Surrogate virus neutralization tests show 90-100% neutralization of ancestral and early VOC in mice and human trial volunteers. EDV-COVID-αGC as a third dose booster neutralized Omicron BA. 4/5. Serum and PBMC analyses reveal long lasting S-specific memory B and T cells. In contrast, control EDVs lacking αGC, did not engage the iNKT/DC pathway resulting in antibody responses unable to neutralize all VOCs and had a reduced B cell memory. The vaccine is lyophilized, stored and transported at room temperature with a shelf-life of over a year.
Author Madrid-Weiss, Jocelyn
Petkovic, Nikolina
Gao, Steven Y
Brahmbhatt, Himanshu
Vanegas, Natasha
Williams, Bryan R G
Visvanathan, Kumar
Amaro-Mugridge, Nancy B
MacDiarmid, Jennifer A
AuthorAffiliation 1 EngeneIC Pty Ltd. , Sydney, NSW , Australia
3 Department of Molecular and Translational Science, Hudson Institute of Medical Research, Monash University Faculty of Medicine, Nursing and Health Sciences , Clayton, VIC , Australia
2 Kumar Visvanathan, Department of Medicine, University of Melbourne , Fitzroy, VIC , Australia
AuthorAffiliation_xml – name: 2 Kumar Visvanathan, Department of Medicine, University of Melbourne , Fitzroy, VIC , Australia
– name: 1 EngeneIC Pty Ltd. , Sydney, NSW , Australia
– name: 3 Department of Molecular and Translational Science, Hudson Institute of Medical Research, Monash University Faculty of Medicine, Nursing and Health Sciences , Clayton, VIC , Australia
Author_xml – sequence: 1
  givenname: Steven Y
  surname: Gao
  fullname: Gao, Steven Y
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 2
  givenname: Nancy B
  surname: Amaro-Mugridge
  fullname: Amaro-Mugridge, Nancy B
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 3
  givenname: Jocelyn
  surname: Madrid-Weiss
  fullname: Madrid-Weiss, Jocelyn
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 4
  givenname: Nikolina
  surname: Petkovic
  fullname: Petkovic, Nikolina
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 5
  givenname: Natasha
  surname: Vanegas
  fullname: Vanegas, Natasha
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 6
  givenname: Kumar
  surname: Visvanathan
  fullname: Visvanathan, Kumar
  organization: Kumar Visvanathan, Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia
– sequence: 7
  givenname: Bryan R G
  surname: Williams
  fullname: Williams, Bryan R G
  organization: Department of Molecular and Translational Science, Hudson Institute of Medical Research, Monash University Faculty of Medicine, Nursing and Health Sciences, Clayton, VIC, Australia
– sequence: 8
  givenname: Jennifer A
  surname: MacDiarmid
  fullname: MacDiarmid, Jennifer A
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
– sequence: 9
  givenname: Himanshu
  surname: Brahmbhatt
  fullname: Brahmbhatt, Himanshu
  organization: EngeneIC Pty Ltd., Sydney, NSW, Australia
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36818474$$D View this record in MEDLINE/PubMed
BookMark eNpVUstu2zAQFIoUTZrmB3ooeOzFLl-ixEuBwunDQNBc2l6JFbWSGMikS0oO3I_oN5eO3SDhgVwsd2Y44LwuznzwWBRvGV0KUesPndts5iWnnC8ZFXWp-IvigiklF4JzefakPi-uUrqjeUkthChfFedC1ayWlbwo_n4HHyyOI1nd_lpfL5gmO7DWeSRTdH2PMREgPuxwJAfF3I-YtsEnJFuYhnvYk20M7ZwhPRlcPyyg65x3056An1wTWoeJ3A_ODsTjPEUY3R8kkBV3EF2eSSR0xAZvMfo3xcsOxoRXp_Oy-Pnl84_Vt8XN7df16tPNwkqmp4Wqq7rCplLaZhelsh3KMpeWCdpI1dpKN0qWrIQS0ILGCkXeGFDsBLZMXBbrI28b4M5so9tA3JsAzjw0QuwNxMnZEY3iKCRUNWvRytrSRitFNYWG1iW3lGeuj0eu7dxssLXoDyafkT6_8W4wfdgZrbnWkmaC9yeCGH7PmCazcenwJ-AxzMnwqtJCZpsqj_LjqI0hpYjdowyj5pAL85ALc8iFOeUig949feAj5H8KxD-Ed7nM
Cites_doi 10.1084/jem.20091706
10.1034/j.1600-065X.2003.00058.x
10.1038/ni.1690
10.1016/j.ccell.2020.02.001
10.1016/j.celrep.2021.109504
10.1194/jlr.D076190
10.1073/pnas.1105774108
10.1016/j.ebiom.2021.103705
10.1146/annurev-immunol-041015-055605
10.1038/s41586-021-03471-w
10.1056/NEJMoa2119451
10.1016/j.immuni.2014.10.004
10.1146/annurev.iy.12.040194.001001
10.1164/rccm.201503-0461LE
10.1084/jem.178.5.1555
10.1038/nbt.1547
10.1016/j.jocn.2015.06.005
10.1080/21645515.2018.1527496
10.1038/bjc.2014.486
10.1084/jem.20020632
10.1016/j.clinbiochem.2021.09.008
10.1038/d41586-021-03552-w
10.1016/j.cell.2022.07.002
10.1002/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q
10.4049/jimmunol.172.9.5154
10.1101/2021.06.28.21259576
10.1016/j.ccr.2007.03.012
10.1038/35876
10.1084/jem.190.8.1123
10.1084/jem.192.11.1545
10.1021/acs.jcim.1c01451
10.1001/jamainternmed.2021.7024
10.4049/jimmunol.171.10.5140
10.1038/s41577-019-0143-6
10.1038/354389a0
10.1084/jem.192.11.1553
10.1016/S1470-2045(17)30621-6
10.1038/icb.2013.55
10.1128/iai.60.8.3345-3359.1992
10.1084/jem.193.12.1373
10.1038/d41586-021-03672-3
10.1038/s41587-020-0631-z
10.1002/immu.200310013
10.1001/jamanetworkopen.2021.31749
10.1126/science.281.5373.96
10.1084/jem.183.5.2303
10.1101/2021.09.06.459005
10.1136/bmj-2021-068632
10.1007/s00018-007-7007-0
10.1038/s41591-020-01194-5
10.3389/fimmu.2018.01496
10.1016/j.xphs.2020.12.006
10.4049/jimmunol.181.3.1767
ContentType Journal Article
Copyright Copyright © 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt.
Copyright © 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt
Copyright_xml – notice: Copyright © 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt.
– notice: Copyright © 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
5PM
DOA
DOI 10.3389/fimmu.2022.1038562
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
Directory of Open Access Journals
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList CrossRef
MEDLINE


Database_xml – sequence: 1
  dbid: DOA
  name: Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 1664-3224
EndPage 1038562
ExternalDocumentID oai_doaj_org_article_62e34a781dec48c0b966090ab0852c02
10_3389_fimmu_2022_1038562
36818474
Genre Research Support, Non-U.S. Gov't
Journal Article
GroupedDBID 53G
5VS
9T4
AAFWJ
AAKDD
ACGFO
ACGFS
ACXDI
ADBBV
ADRAZ
AENEX
AFPKN
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BCNDV
CGR
CUY
CVF
DIK
EBS
ECM
EIF
EMOBN
GROUPED_DOAJ
GX1
HYE
IAO
IEA
IHR
IHW
IPNFZ
KQ8
M48
M~E
NPM
OK1
PGMZT
RIG
RNS
RPM
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c419t-68787eb769c47456cfe45c47c130b46dc79b64515a5aeca9e7e39e71a0ef3ed13
IEDL.DBID RPM
ISSN 1664-3224
IngestDate Tue Oct 22 15:12:40 EDT 2024
Tue Sep 17 21:33:56 EDT 2024
Sat Oct 05 06:17:54 EDT 2024
Fri Nov 22 00:14:08 EST 2024
Sat Sep 28 08:17:28 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords COVID-19
iNKT activation
memory T cell
nanocell vaccine
variants of concern
memory B cell
Language English
License Copyright © 2023 Gao, Amaro-Mugridge, Madrid-Weiss, Petkovic, Vanegas, Visvanathan, Williams, MacDiarmid and Brahmbhatt.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c419t-68787eb769c47456cfe45c47c130b46dc79b64515a5aeca9e7e39e71a0ef3ed13
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by: Luciana C. C. Leite, Butantan Institute, Brazil
Reviewed by: Fabio Fiorino, LUM University Giuseppe Degennaro, Italy; Nejat Duzgunes, University of the Pacific, United States
These authors have contributed equally to this work and share first authorship
This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology
These authors contributed equally to senior authorship
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929940/
PMID 36818474
PQID 2779344566
PQPubID 23479
PageCount 1
ParticipantIDs doaj_primary_oai_doaj_org_article_62e34a781dec48c0b966090ab0852c02
pubmedcentral_primary_oai_pubmedcentral_nih_gov_9929940
proquest_miscellaneous_2779344566
crossref_primary_10_3389_fimmu_2022_1038562
pubmed_primary_36818474
PublicationCentury 2000
PublicationDate 2023-01-27
PublicationDateYYYYMMDD 2023-01-27
PublicationDate_xml – month: 01
  year: 2023
  text: 2023-01-27
  day: 27
PublicationDecade 2020
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
PublicationTitle Frontiers in immunology
PublicationTitleAlternate Front Immunol
PublicationYear 2023
Publisher Frontiers Media S.A
Publisher_xml – name: Frontiers Media S.A
References Avery (B51) 2008; 181
Bergman (B7) 2021; 74
Kao (B16) 2015; 191
Sartorius (B22) 2018; 9
Gunn (B45) 1998; 391
MacDiarmid (B14) 2007; 11
Hu (B37) 2011; 108
Hermans (B28) 2003; 171
Eertwegh (B32) 1993; 178
Andrews (B1) 2022; 386
Sagnella (B25) 2020; 37
Garside (B34) 1998; 281
Uriu (B6) 2021
Tan (B23) 2020; 38
Bauquet (B40) 2009; 10
MacDiarmid (B15) 2009; 27
Ansel (B46) 1999; 190
Bergamaschi (B27) 2021; 36
Lee (B9) 2022; 376
Krammer (B11) 2019; 19
Singh (B20) 2014; 111
Haidar (B5) 2021
Breitfeld (B49) 2000; 192
Avery (B52) 2010; 207
Sun (B10) 2022; 182
von Gerichten (B21) 2017; 58
Jacob (B43) 1991; 354
Dolton (B4) 2022; 185
Ewer (B31) 2021; 27
MacLennan (B42) 2003; 194
Schaerli (B47) 2000; 192
Cele (B54) 2021; 593
Crommelin (B13) 2021; 110
Whittle (B18) 2015; 22
MacLennan (B44) 1994; 12
Crotty (B41) 2014; 41
Chen (B8) 2021; 4
B53
Callaway (B3) 2021
Callaway (B2) 2021; 600
Su (B19) 1992; 60
Pène (B50) 2004; 172
Jung (B24) 2021; 98
Bricard (B26) 2007; 64
Billeskov (B30) 2019; 15
Bonhagen (B38) 2003; 33
Toellner (B33) 1996; 183
Löhning (B39) 2003; 197
Chen (B12) 2022; 62
van Zandwijk (B17) 2017; 18
Kim (B48) 2001; 193
Ma (B35) 2014; 92
Vinuesa (B29) 2016; 34
Beier (B36) 2000; 30
References_xml – volume: 207
  year: 2010
  ident: B52
  article-title: B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
  publication-title: J Exp Med
  doi: 10.1084/jem.20091706
  contributor:
    fullname: Avery
– volume: 194
  start-page: 8
  year: 2003
  ident: B42
  article-title: Extrafollicular antibody responses
  publication-title: Immunol Rev
  doi: 10.1034/j.1600-065X.2003.00058.x
  contributor:
    fullname: MacLennan
– volume: 10
  year: 2009
  ident: B40
  article-title: The costimulatory molecule ICOS regulates the expression of c-maf and IL-21 in the development of follicular T helper cells and TH-17 cells
  publication-title: Nat Immunol
  doi: 10.1038/ni.1690
  contributor:
    fullname: Bauquet
– volume: 37
  start-page: 354
  year: 2020
  ident: B25
  article-title: Cyto-Immuno-Therapy for cancer: A pathway elicited by tumor-targeted, tytotoxic drug-packaged bacterially derived nanocells
  publication-title: Cancer Cell
  doi: 10.1016/j.ccell.2020.02.001
  contributor:
    fullname: Sagnella
– volume: 36
  start-page: 109504
  year: 2021
  ident: B27
  article-title: Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2021.109504
  contributor:
    fullname: Bergamaschi
– volume: 58
  year: 2017
  ident: B21
  article-title: Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals
  publication-title: J Lipid Res
  doi: 10.1194/jlr.D076190
  contributor:
    fullname: von Gerichten
– volume: 108
  year: 2011
  ident: B37
  article-title: Noncanonical NF-kappaB regulates inducible costimulator (ICOS) ligand expression and T follicular helper cell development
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1105774108
  contributor:
    fullname: Hu
– volume: 74
  start-page: 103705
  year: 2021
  ident: B7
  article-title: Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
  publication-title: EBioMedicine
  doi: 10.1016/j.ebiom.2021.103705
  contributor:
    fullname: Bergman
– volume: 34
  year: 2016
  ident: B29
  article-title: Follicular helper T cells
  publication-title: Annu Rev Immunol
  doi: 10.1146/annurev-immunol-041015-055605
  contributor:
    fullname: Vinuesa
– volume: 593
  year: 2021
  ident: B54
  article-title: Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
  publication-title: Nature
  doi: 10.1038/s41586-021-03471-w
  contributor:
    fullname: Cele
– volume: 386
  year: 2022
  ident: B1
  article-title: Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant
  publication-title: N Engl J Med
  doi: 10.1056/NEJMoa2119451
  contributor:
    fullname: Andrews
– volume: 41
  year: 2014
  ident: B41
  article-title: T Follicular helper cell differentiation, function, and roles in disease
  publication-title: Immunity
  doi: 10.1016/j.immuni.2014.10.004
  contributor:
    fullname: Crotty
– volume: 12
  year: 1994
  ident: B44
  article-title: Germinal centers
  publication-title: Annu Rev Immunol
  doi: 10.1146/annurev.iy.12.040194.001001
  contributor:
    fullname: MacLennan
– volume: 191
  year: 2015
  ident: B16
  article-title: A significant metabolic and radiological response after a novel targeted microRNA-based treatment approach in malignant pleural mesothelioma
  publication-title: Am J Respir Crit Care Med
  doi: 10.1164/rccm.201503-0461LE
  contributor:
    fullname: Kao
– volume: 178
  year: 1993
  ident: B32
  article-title: In vivo CD40-gp39 interactions are essential for thymus-dependent humoral immunity. i. In vivo expression of CD40 ligand, cytokines, and antibody production delineates sites of cognate T-b cell interactions
  publication-title: J Exp Med
  doi: 10.1084/jem.178.5.1555
  contributor:
    fullname: Eertwegh
– volume: 27
  year: 2009
  ident: B15
  article-title: Sequential treatment of drug-resistant tumors with targeted minicells containing siRNA or a cytotoxic drug
  publication-title: Nat Biotechnol
  doi: 10.1038/nbt.1547
  contributor:
    fullname: MacDiarmid
– volume: 22
  year: 2015
  ident: B18
  article-title: First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma
  publication-title: J Clin Neurosci
  doi: 10.1016/j.jocn.2015.06.005
  contributor:
    fullname: Whittle
– volume: 15
  year: 2019
  ident: B30
  article-title: The effect of antigen dose on T cell-targeting vaccine outcome
  publication-title: Hum Vaccin Immunother
  doi: 10.1080/21645515.2018.1527496
  contributor:
    fullname: Billeskov
– volume: 111
  year: 2014
  ident: B20
  article-title: Direct incorporation of the NKT-cell activator alpha-galactosylceramide into a recombinant listeria monocytogenes improves breast cancer vaccine efficacy
  publication-title: Br J Cancer
  doi: 10.1038/bjc.2014.486
  contributor:
    fullname: Singh
– volume: 197
  year: 2003
  ident: B39
  article-title: Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10
  publication-title: J Exp Med
  doi: 10.1084/jem.20020632
  contributor:
    fullname: Löhning
– volume: 98
  year: 2021
  ident: B24
  article-title: Analytical and clinical performance of cPass neutralizing antibodies assay
  publication-title: Clin Biochem
  doi: 10.1016/j.clinbiochem.2021.09.008
  contributor:
    fullname: Jung
– year: 2021
  ident: B3
  article-title: Heavily mutated omicron variant puts scientists on alert
  publication-title: Nature
  doi: 10.1038/d41586-021-03552-w
  contributor:
    fullname: Callaway
– volume: 185
  start-page: 2936
  year: 2022
  ident: B4
  article-title: Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope
  publication-title: Cell
  doi: 10.1016/j.cell.2022.07.002
  contributor:
    fullname: Dolton
– volume: 30
  year: 2000
  ident: B36
  article-title: Induction, binding specificity and function of human ICOS
  publication-title: Eur J Immunol
  doi: 10.1002/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q
  contributor:
    fullname: Beier
– volume: 172
  year: 2004
  ident: B50
  article-title: Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human b cells
  publication-title: J Immunol (Baltimore Md 1950)
  doi: 10.4049/jimmunol.172.9.5154
  contributor:
    fullname: Pène
– year: 2021
  ident: B5
  article-title: Immunogenicity of COVID-19 vaccination in immunocompromised patients: An observational, prospective cohort study interim analysis
  publication-title: medRxiv
  doi: 10.1101/2021.06.28.21259576
  contributor:
    fullname: Haidar
– volume: 11
  year: 2007
  ident: B14
  article-title: Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics
  publication-title: Cancer Cell
  doi: 10.1016/j.ccr.2007.03.012
  contributor:
    fullname: MacDiarmid
– volume: 391
  start-page: 799
  year: 1998
  ident: B45
  article-title: A b-cell-homing chemokine made in lymphoid follicles activates burkitt's lymphoma receptor-1
  publication-title: Nature
  doi: 10.1038/35876
  contributor:
    fullname: Gunn
– volume: 190
  year: 1999
  ident: B46
  article-title: In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines
  publication-title: J Exp Med
  doi: 10.1084/jem.190.8.1123
  contributor:
    fullname: Ansel
– volume: 192
  year: 2000
  ident: B49
  article-title: Follicular b helper T cells express CXC chemokine receptor 5, localize to b cell follicles, and support immunoglobulin production
  publication-title: J Exp Med
  doi: 10.1084/jem.192.11.1545
  contributor:
    fullname: Breitfeld
– volume: 62
  year: 2022
  ident: B12
  article-title: Omicron variant (B.1.1.529): Infectivity, vaccine breakthrough, and antibody resistance
  publication-title: J Chem Inf Model
  doi: 10.1021/acs.jcim.1c01451
  contributor:
    fullname: Chen
– volume: 182
  year: 2022
  ident: B10
  article-title: Association between immune dysfunction and COVID-19 breakthrough infection after SARS-CoV-2 vaccination in the US
  publication-title: JAMA Intern Med
  doi: 10.1001/jamainternmed.2021.7024
  contributor:
    fullname: Sun
– volume: 171
  year: 2003
  ident: B28
  article-title: NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells
  publication-title: J Immunol (Baltimore Md: 1950)
  doi: 10.4049/jimmunol.171.10.5140
  contributor:
    fullname: Hermans
– volume: 19
  year: 2019
  ident: B11
  article-title: The human antibody response to influenza a virus infection and vaccination
  publication-title: Nat Rev Immunol
  doi: 10.1038/s41577-019-0143-6
  contributor:
    fullname: Krammer
– volume: 354
  year: 1991
  ident: B43
  article-title: Intraclonal generation of antibody mutants in germinal centres
  publication-title: Nature
  doi: 10.1038/354389a0
  contributor:
    fullname: Jacob
– volume: 192
  year: 2000
  ident: B47
  article-title: CXC chemokine receptor 5 expression defines follicular homing T cells with b cell helper function
  publication-title: J Exp Med
  doi: 10.1084/jem.192.11.1553
  contributor:
    fullname: Schaerli
– volume: 18
  year: 2017
  ident: B17
  article-title: Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study
  publication-title: Lancet Oncol
  doi: 10.1016/S1470-2045(17)30621-6
  contributor:
    fullname: van Zandwijk
– volume: 92
  start-page: 64
  year: 2014
  ident: B35
  article-title: Human T follicular helper (Tfh) cells and disease
  publication-title: Immunol Cell Biol
  doi: 10.1038/icb.2013.55
  contributor:
    fullname: Ma
– volume: 60
  year: 1992
  ident: B19
  article-title: Construction of stable LamB-shiga toxin b subunit hybrids: analysis of expression in salmonella typhimurium aroA strains and stimulation of b subunit-specific mucosal and serum antibody responses
  publication-title: Infection immunity
  doi: 10.1128/iai.60.8.3345-3359.1992
  contributor:
    fullname: Su
– volume: 193
  year: 2001
  ident: B48
  article-title: Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells
  publication-title: J Exp Med
  doi: 10.1084/jem.193.12.1373
  contributor:
    fullname: Kim
– volume: 600
  year: 2021
  ident: B2
  article-title: Omicron likely to weaken COVID vaccine protection
  publication-title: Nature
  doi: 10.1038/d41586-021-03672-3
  contributor:
    fullname: Callaway
– volume: 38
  year: 2020
  ident: B23
  article-title: A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction
  publication-title: Nat Biotechnol
  doi: 10.1038/s41587-020-0631-z
  contributor:
    fullname: Tan
– volume: 33
  start-page: 392
  year: 2003
  ident: B38
  article-title: ICOS+ Th cells produce distinct cytokines in different mucosal immune responses
  publication-title: Eur J Immunol
  doi: 10.1002/immu.200310013
  contributor:
    fullname: Bonhagen
– volume: 4
  year: 2021
  ident: B8
  article-title: Immunogenicity rates after SARS-CoV-2 vaccination in people with end-stage kidney disease: A systematic review and meta-analysis
  publication-title: JAMA Netw Open
  doi: 10.1001/jamanetworkopen.2021.31749
  contributor:
    fullname: Chen
– volume: 281
  year: 1998
  ident: B34
  article-title: Visualization of specific b and T lymphocyte interactions in the lymph node
  publication-title: Sci (New York NY)
  doi: 10.1126/science.281.5373.96
  contributor:
    fullname: Garside
– volume: 183
  year: 1996
  ident: B33
  article-title: Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific b cell activation
  publication-title: J Exp Med
  doi: 10.1084/jem.183.5.2303
  contributor:
    fullname: Toellner
– year: 2021
  ident: B6
  article-title: Ineffective neutralization of the SARS-CoV-2 mu variant by convalescent and vaccine sera
  publication-title: bioRxiv
  doi: 10.1101/2021.09.06.459005
  contributor:
    fullname: Uriu
– volume: 376
  year: 2022
  ident: B9
  article-title: Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis
  publication-title: BMJ
  doi: 10.1136/bmj-2021-068632
  contributor:
    fullname: Lee
– volume: 64
  year: 2007
  ident: B26
  article-title: Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity
  publication-title: Cell Mol Life sciences: CMLS
  doi: 10.1007/s00018-007-7007-0
  contributor:
    fullname: Bricard
– volume: 27
  year: 2021
  ident: B31
  article-title: T Cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
  publication-title: Nat Med
  doi: 10.1038/s41591-020-01194-5
  contributor:
    fullname: Ewer
– volume: 9
  year: 2018
  ident: B22
  article-title: Vectorized delivery of alpha-galactosylceramide and tumor antigen on filamentous bacteriophage fd induces protective immunity by enhancing tumor-specific T cell response
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2018.01496
  contributor:
    fullname: Sartorius
– volume: 110
  start-page: 997
  year: 2021
  ident: B13
  article-title: Addressing the cold reality of mRNA vaccine stability
  publication-title: J Pharm Sci
  doi: 10.1016/j.xphs.2020.12.006
  contributor:
    fullname: Crommelin
– volume: 181
  year: 2008
  ident: B51
  article-title: IL-21-induced isotype switching to IgG and IgA by human naive b cells is differentially regulated by IL-4
  publication-title: J Immunol (Baltimore Md: 1950)
  doi: 10.4049/jimmunol.181.3.1767
  contributor:
    fullname: Avery
– ident: B53
SSID ssj0000493335
Score 2.3902872
Snippet Most current anti-viral vaccines elicit a humoral and cellular immune response the pathway of phagocytic cell mediated viral antigen presentation to B and T...
Most current anti-viral vaccines elicit a humoral and cellular immune response via the pathway of phagocytic cell mediated viral antigen presentation to B and...
Most current anti-viral vaccines elicit a humoral and cellular immune response via the pathway of phagocytic cell mediated viral antigen presentation to B and...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
StartPage 1038562
SubjectTerms Animals
Antigen Presentation
COVID-19
COVID-19 Vaccines
Humans
Immunology
iNKT activation
Leukocytes, Mononuclear
memory B cell
memory T cell
Mice
nanocell vaccine
SARS-CoV-2
variants of concern
SummonAdditionalLinks – databaseName: Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nb9QwELVQpUpcEC1foYCMxA1FdWzHiY-lUBUk4EJRb5ZjT9ggmlTb3a2WH8FvZiZOq12ExIVLFDmR7MyMPW-c8RvGXtlCeUC_lPvoRa6lwHXQRJtbEY1VZYx6JHv--MmcnukP5-X5RqkvyglL9MBJcIdGgtK-QlgFQddBNEQnaYVvECvIMNFICrkRTH1PuFcpVaZTMhiF2cO2u7hYYjwo5cgJXhq55YlGwv6_ocw_kyU3vM_JfXZvgo38KA13j92Bfp_tpkKS6wfsFy6SA-3B8-PPX9-_zQvLVz7QP3O-wPD7G2I87nk_rOAHpxFi-zwlxwKnmsTXfs0vR-5X9GScKIxz37YdTvc1R9F3zUDJhvx61oUZ72E5bo_8BO6xxxVG25RMw4eWBzoEOe8fsrOTd1-OT_Op0kIedGEXualx3kJTGRt0hZAqtKBLvA3o4RptYqhsYzRCH196CN5CBQovhRfQKoiFesR2-qGHJ4yrIHwRYixDbXQMoo5Q16qmyMVjKBky9vpG6u4yEWo4DERIR27UkSMduUlHGXtDirl9k8iwxwY0ETeZiPuXiWTs5Y1aHU4e0obvYVheOVnh8qTxg03GHic133alDGIZlEbGqi0D2BrL9pO-m40E3RYxp9Xi6f8Y_AG7SxXuaddHVs_YzmK-hOeIgxbNi9HkfwMLdAgP
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Scholars Portal Open Access Journals
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Nb9QwELWqIiQuiG-WAjISN2RwYseJDxWCQlWQChcW9RY59qQb1CYl3d2y_Ah-MzNOtmJROXCJoiRKHD975o0zecPYc5soB-iXhAtOCp1KtIMmWGFlMFZlIego9nz4yRxM9cej7GiLrcsdjR14fmVoR_Wkpv3Jyx_fV69xwu9SxIn-9lXdnJ4uMNRL0yj3nZFJvpaiZ6QUr8OR7n8b2LBSseZmYowWOJb18B_NP26z4auipP9VPPTvdMo__NP-LXZzJJb8zTASbrMtaO-w60OpydVd9gvNaEer9Hzv89cP70Ri-dJ5-qrO5xigHyML5I633RJOOLUQj_dD-ixwqlp84Vb8LKrDoq_jJHIsXF03aBBWHMFpqo7SEfnFrPEz3sIiLqD8BO7wiUuMxyndhnc19_SbZN_eY9P991_2DsRYi0F4ndi5MAXObKhyY73OkXT5GnSGux59YKVN8LmtjEZy5DIH3lnIQeEmcRJqBSFR99l227XwkHHlpUt8CJkvjA5eFgGKQhUU2zgMNv2EvVj3enk2SG6UGKoQRmXEqCSMyhGjCXtLwFxeSXLZ8UDXH5fj7CtNCkq7HLk5eF14WZEmqZWuQsKZeok3ebaGtcTpRWi4FrrFeZnmaMA0vrCZsAcDzJePUgbZDvbGhOUbA2CjLZtn2mYWJbwtslKr5aP_etUddoOK3dMCUJo_ZtvzfgFPkBLNq6dxnP8GMlEKwg
  priority: 102
  providerName: Scholars Portal
Title Nanocell COVID-19 vaccine triggers a novel immune response pathway producing high-affinity antibodies which neutralize all variants of concern
URI https://www.ncbi.nlm.nih.gov/pubmed/36818474
https://search.proquest.com/docview/2779344566
https://pubmed.ncbi.nlm.nih.gov/PMC9929940
https://doaj.org/article/62e34a781dec48c0b966090ab0852c02
Volume 13
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELe2SUi8oI3PwpiMxBvK6sSOEz9CYQykAg8M9S1yzpc1aE2qru1U_gj-Zs5OOq2IJ16sKF92fGff7y7nnxl7bWJpkexSZJ0VkUoEzYPamcgIp41MnVOB7Hn8RZ9fqM-TdLLH0u1amJC0D2V92lzNTpt6GnIr5zMYbvPEht_GI0M23Sgx3Gf7ZH7vuOg_O8grpUy7BTLkgJlhVc9mK3IFkyTQgac62TFCgav_XwDz7zzJO4bn7JA96BEjf9u17IjtYfOQ3ev2kNw8Yr9pfmx9-J2Pvv749D6KDV9b8L_L-ZI870uCd9zypl3jFfctpPOLLi8Wud-O-MZu-DzQvpIR4569OLJVVdNI33Dq9bpsfZ4hv5nWMOUNrkJk5BdySzWuydH2eTS8rTj49Y-L5jG7OPvwfXQe9ZssRKBis4x0TkMWy0wbUBmhKahQpXQIZNxKpR1kptSKUI9NLYI1mKGkIrYCK4kulk_YQdM2-IxxCcLG4FwKuVYORO4wz2XunRZLXiQM2JttrxfzjkujIB_Ey6gIMiq8jIpeRgP2zgvm9k7Pgx1OtIvLoteGQicolc0IdCOoHETpyUaNsCUhyQQEveTVVqwFjRsvDdtgu7oukoxmJkUfrAfsaSfm26qkJhhDvTFg2Y4C7LRl9wqpauDm7lXz-X8_-YLd9zva-yhPkh2zg-VihS8J9yzLkxAvoPLjJKZyrPKToPl_AKRFCm0
link.rule.ids 230,314,727,780,784,864,885,2102,24318,27924,27925,53791,53793
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELfGEIIXxDcdX0biDWV1YseJH0dh6mAdPGxob5ZjX9agNam6tlP3R-xv3tlJpxXxxEsUOR92fGff75zz7wj5pGJuAO1SZJxhkUgYzoPSqUgxJxVPnROB7Hl0JIcn4vtperpF0vVemBC0b4tqtz6f7NbVOMRWTie2v44T6_8aDRTadCVY_x65n_JMxXec9D8t6OWcp-0WGXTBVL-sJpMFOoNJEgjBU5lsmKHA1v8viPl3pOQd07P_hDzuMCPda9v2lGxB_Yw8aLNIrp6Ta5whG78ATwc_fx98jWJFl8b6H-Z0jr73GQI8amjdLOGc-hZi-ayNjAXqExJfmhWdBuJXNGPU8xdHpiwrHOsriv1eFY2PNKSX48qOaQ2LsDZyBdRgjUt0tX0kDW1Kav0OyFn9gpzsfzseDKMuzUJkRazmkcxx0EKRSWVFhnjKliBSPLVo3gohnc1UIQXiHpMasEZBBhwPsWFQcnAxf0m266aG14Ryy0xsnUttLoWzLHeQ5zz3botBP9L2yOd1r-tpy6ah0QvxMtJBRtrLSHcy6pEvXjC3d3om7FDQzM50pw9aJsCFyRB2gxW5ZYWnG1XMFIglE8vwJR_XYtU4crw0TA3N4kInGc5NAj9Y9sirVsy3VXGJQAZ7o0eyDQXYaMvmFVTWwM7dKefOfz_5gTwcHo8O9eHB0Y835JHPb-_XfJLsLdmezxbwDlHQvHgfdP4G_UELAg
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwELagCMSl4lm2vIzEDaVxYseJj7Bl1QItPVDUm-WMnW5QN1ktu1stP4LfzNjJVruIE5coch52PGPPN874G0LeqoQbh3YpMtawSKQM50FpVaSYlYpn1opA9nxyKo_OxaeL7GIj1VcI2oeyPmiuJgdNPQ6xldMJxOs4sfjsZKjQpivB4qmt4tvkTsZRyTYc9R8d8OWcZ902GXTDVFzVk8kCHcI0DaTgmUy3TFFg7P8XzPw7WnLD_IwekN0eN9L3XfsekluueUTudpkkV4_Jb5wlW78IT4dfvx8fRomiSwP-pzmdo_99iSCPGtq0S3dFfQuxfNZFxzrqkxJfmxWdBvJXNGXUcxhHpqpqHO8rin1fl62PNqTX4xrGtHGLsD7yy1GDNS7R3fbRNLStKPhdkLPmCTkfffw2PIr6VAsRiETNI1ngwHVlLhWIHDEVVE5keApo4kohLeSqlAKxj8mMA6Nc7jgeEsNcxZ1N-FOy07SNe0YoB2YSsDaDQgoLrLCuKHjhXReDviQMyLt1r-tpx6ih0RPxMtJBRtrLSPcyGpAPXjA3d3o27FDQzi51rxNapo4LkyP0diAKYKWnHFXMlIgnU2D4kjdrsWocPV4apnHt4qdOc1QdgR8sB2SvE_NNVVwimMHeGJB8SwG22rJ9BRU2MHT3Crr_30--JvfODkf6y_Hp5-fkvk9x75d90vwF2ZnPFu4lAqF5-Sqo_B-48wwV
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Nanocell+COVID-19+vaccine+triggers+a+novel+immune+response+pathway+producing+high-affinity+antibodies+which+neutralize+all+variants+of+concern&rft.jtitle=Frontiers+in+immunology&rft.au=Gao%2C+Steven+Y.&rft.au=Amaro-Mugridge%2C+Nancy+B.&rft.au=Madrid-Weiss%2C+Jocelyn&rft.au=Petkovic%2C+Nikolina&rft.date=2023-01-27&rft.issn=1664-3224&rft.eissn=1664-3224&rft.volume=13&rft_id=info:doi/10.3389%2Ffimmu.2022.1038562&rft.externalDBID=n%2Fa&rft.externalDocID=10_3389_fimmu_2022_1038562
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1664-3224&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1664-3224&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1664-3224&client=summon