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Article ; Online: Dengue virus 4/2 envelope domain chimeric virus panel maps type-specific responses against dengue serotype 2.

Zhu, Deanna R / Rajesh, Alecia J / Meganck, Rita M / Young, Ellen F / Munt, Jennifer E / Tse, Victor L / Yount, Boyd / Conrad, Helen / White, Laura / Henein, Sandra / DeSilva, Aravinda M / Baric, Ralph S

mBio

2023 Volume 14, Issue 5, Page(s) e0081823

Abstract: Importance: The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever ... ...

Abstract	Importance: The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever to life-threatening shock. Despite the availability of licensed vaccines, a comprehensive understanding of antibodies that target the viral envelope protein and protect from infection remains incomplete. In this manuscript, we develop a panel of recombinant viruses that graft each envelope domain of DENV2 onto the DENV4 envelope glycoprotein, revealing protein interactions important for virus viability. Furthermore, we map neutralizing antibody responses after primary DENV2 natural infection and a human challenge model to distinct domains on the viral envelope protein. The panel of recombinant viruses provides a new tool for dissecting the E domain-specific targeting of protective antibody responses, informing future DENV vaccine design.
MeSH term(s)	Humans ; Dengue Virus ; Dengue ; Antibodies, Viral ; Viral Envelope Proteins/genetics ; Serogroup ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Viral ; Viral Envelope Proteins ; Antibodies, Neutralizing
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00818-23
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Article ; Online: Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees.

Martinez, David R / Yount, Boyd / Nivarthi, Usha / Munt, Jennifer E / Delacruz, Matthew J / Whitehead, Stephen S / Durbin, Anna P / de Silva, Aravinda M / Baric, Ralph S

Cell reports

2021 Volume 33, Issue 1, Page(s) 108226

Abstract: Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) ...

Abstract	Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) proteins of DENV2 on vaccine performance. We generated a recombinant DENV2 genotype variant panel with contemporary prM and E isolates that are representative of global genetic diversity. The DENV2 genotype variants differ in growth kinetics, morphology, and virion stability. Importantly, the DENV2 genotypic variants are differentially neutralized by monoclonal antibodies, polyclonal serum neutralizing antibodies from DENV2-infected human subjects, and vaccine-elicited antibody responses from the TV003 NIH DENV2 monovalent and DENV tetravalent vaccines. We conclude that DENV2 prM and E genetic diversity significantly modulates antibody neutralization activity. These findings have important implications for dengue vaccines, which are being developed under the assumption that intraserotype variation has minimal impact on neutralizing antibodies.
MeSH term(s)	Antibodies, Neutralizing/metabolism ; Antigenic Variation ; Dengue Virus/genetics ; Genotype ; Humans ; Vaccination/methods
Chemical Substances	Antibodies, Neutralizing
Language	English
Publishing date	2021-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.108226
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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: Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2.

Feng, Yupeng / Yuan, Meng / Powers, John M / Hu, Mengyun / Munt, Jennifer E / Arunachalam, Prabhu S / Leist, Sarah R / Bellusci, Lorenza / Adams, Lily E / Sundaramurthy, Sumana / Shirreff, Lisa M / Mallory, Michael L / Scooby, Trevor D / Moreno, Alberto / O'Hagan, Derek T / Kleanthous, Harry / Villinger, Francois J / Veesler, David / King, Neil P /

Suthar, Mehul S / Khurana, Surender / Baric, Ralph S / Wilson, Ian A / Pulendran, Bali

bioRxiv : the preprint server for biology

2023

Abstract: The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we ... ...

Abstract	The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (∼4.4%) antibodies isolated at 1.4∼6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies. One sentence summary: Extremely potent pan-sarbecovirus neutralizing antibodies.
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.19.524784
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Article: Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.

medRxiv : the preprint server for health sciences

2023

Abstract: Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to ... ...

Abstract	Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity. One sentence summary: SARS-CoV-2 point-of-care antibody tests are valuable and easy-to-access tools to inform inadequate humoral immunity and to support informed decision-making regarding the current and future booster vaccination.
Language	English
Publishing date	2023-04-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.03.23287498
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Article ; Online: A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity.

Young, Ellen / Yount, Boyd / Pantoja, Petraleigh / Henein, Sandra / Meganck, Rita M / McBride, Jennifer / Munt, Jennifer E / Baric, Thomas J / Zhu, Deanna / Scobey, Trevor / Dong, Stephanie / Tse, Longping V / Martinez, Melween I / Burgos, Armando G / Graham, Rachel L / White, Laura / DeSilva, Aravinda / Sariol, Carlos A / Baric, Ralph S

Nature communications

2023 Volume 14, Issue 1, Page(s) 1371

Abstract: The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more ...

Abstract	The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective immunity. Among the number of vaccine candidates in clinical trials, only Dengvaxia is licensed for use in DENV seropositive individuals. To simplify live-virus vaccine design, we identify co-evolutionary constraints inherent in flavivirus virion assembly and design chimeric viruses to replace domain II (EDII) of the DENV2 envelope (E) glycoprotein with EDII from DENV4. The chimeric DENV2/4EDII virus replicates efficiently in vitro and in vivo. In male macaques, a single inoculation of DENV2/4EDII induces type-specific neutralizing antibodies to both DENV2 and DENV4, thereby providing a strategy to simplify DENV vaccine design by utilizing a single bivalent E glycoprotein immunogen for two DENV serotypes.
MeSH term(s)	Male ; Humans ; Dengue Virus/genetics ; Antibodies, Viral ; Serogroup ; Viral Envelope Proteins/genetics ; Antibodies, Neutralizing ; Dengue
Chemical Substances	Antibodies, Viral ; Viral Envelope Proteins ; Antibodies, Neutralizing
Language	English
Publishing date	2023-03-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-36702-x
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Article ; Online: Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.

Cell host & microbe

2023 Volume 31, Issue 11, Page(s) 1850–1865.e5

Abstract: The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or ...

Abstract	The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear. To identify the primary DENV3 nAb targets in sera after natural infection or vaccination, chimeric DENV1 recombinant encoding DENV3 EDI, EDII, or EDIII were generated. DENV3 EDII is the principal target of TS polyclonal nAb responses and encodes two or more neutralizing epitopes. In contrast, some were individuals vaccinated with a DENV3 monovalent vaccine-elicited serum TS nAbs targeting each ED in a subject-dependent fashion, with an emphasis on EDI and EDIII. Vaccine responses were also sensitive to DENV3 genotypic variation. This DENV1/3 panel allows the measurement of serum ED TS nAbs, revealing differences in TS nAb immunity after natural infection or vaccination.
MeSH term(s)	Humans ; Antibodies, Viral ; Dengue Virus ; Antibodies, Neutralizing ; Dengue Vaccines ; Viral Envelope Proteins/genetics ; Glycoproteins ; Vaccination ; Dengue
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing ; Dengue Vaccines ; Viral Envelope Proteins ; Glycoproteins
Language	English
Publishing date	2023-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2023.10.004
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Article ; Online: Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection.

Tse, Longping V / Meganck, Rita M / Araba, Kenza C / Yount, Boyd L / Shaffer, Kendall M / Hou, Yixuan J / Munt, Jennifer E / Adams, Lily E / Wykoff, Jason A / Morowitz, Jeremy M / Dong, Stephanie / Magness, Scott T / Marzluff, William F / Gonzalez, Liara M / Ehre, Camille / Baric, Ralph S

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 18, Page(s) e2118126119

Abstract: Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human ... ...

Abstract	Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.
MeSH term(s)	Alphacoronavirus/genetics ; Animals ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Coronavirus Infections/epidemiology ; Swine ; Swine Diseases
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2118126119
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Zs.A 1148: Show issues

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Article ; Online: Coronavirus Immunotherapeutic Consortium Database.

Mahita, Jarjapu / Ha, Brendan / Gambiez, Anais / Schendel, Sharon L / Li, Haoyang / Hastie, Kathryn M / Dennison, S Moses / Li, Kan / Kuzmina, Natalia / Periasamy, Sivakumar / Bukreyev, Alexander / Munt, Jennifer E / Osei-Twum, Mary / Atyeo, Caroline / Overton, James A / Vita, Randi / Guzman-Orozco, Hector / Mendes, Marcus / Kojima, Mari /

Halfmann, Peter J / Kawaoka, Yoshihiro / Alter, Galit / Gagnon, Luc / Baric, Ralph S / Tomaras, Georgia D / Germann, Tim / Bedinger, Daniel / Greenbaum, Jason A / Saphire, Erica Ollmann / Peters, Bjoern

Database : the journal of biological databases and curation

2023 Volume 2023

Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen multiple anti-SARS-CoV-2 antibodies being generated globally. It is difficult, however, to assemble a useful compendium ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seen multiple anti-SARS-CoV-2 antibodies being generated globally. It is difficult, however, to assemble a useful compendium of these biological properties if they are derived from experimental measurements performed at different sites under different experimental conditions. The Coronavirus Immunotherapeutic Consortium (COVIC) circumvents these issues by experimentally testing blinded antibodies side by side for several functional activities. To collect these data in a consistent fashion and make it publicly available, we established the COVIC database (COVIC-DB, https://covicdb.lji.org/). This database enables systematic analysis and interpretation of this large-scale dataset by providing a comprehensive view of various features such as affinity, neutralization, in vivo protection and effector functions for each antibody. Interactive graphs enable direct comparisons of antibodies based on select functional properties. We demonstrate how the COVIC-DB can be utilized to examine relationships among antibody features, thereby guiding the design of therapeutic antibody cocktails. Database URL https://covicdb.lji.org/.
MeSH term(s)	Humans ; COVID-19/epidemiology ; SARS-CoV-2 ; Antibodies, Viral ; Immunotherapy
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2496706-3
ISSN	1758-0463 ; 1758-0463
ISSN (online)	1758-0463
ISSN	1758-0463
DOI	10.1093/database/baac112
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Article ; Online: Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine.

Feng, Yupeng / Yuan, Meng / Powers, John M / Hu, Mengyun / Munt, Jennifer E / Arunachalam, Prabhu S / Leist, Sarah R / Bellusci, Lorenza / Kim, JungHyun / Sprouse, Kaitlin R / Adams, Lily E / Sundaramurthy, Sumana / Zhu, Xueyong / Shirreff, Lisa M / Mallory, Michael L / Scobey, Trevor D / Moreno, Alberto / O'Hagan, Derek T / Kleanthous, Harry /

Villinger, Francois J / Veesler, David / King, Neil P / Suthar, Mehul S / Khurana, Surender / Baric, Ralph S / Wilson, Ian A / Pulendran, Bali

Science translational medicine

2023 Volume 15, Issue 695, Page(s) eadg7404

Abstract: 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 of countermeasures that provide broad protection against SARS-CoV-2 and ... ...

Abstract	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 of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus-pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.
MeSH term(s)	Animals ; Humans ; Mice ; Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; Severe acute respiratory syndrome-related coronavirus ; Macaca ; SARS-CoV-2 ; COVID-19/prevention & control ; Immunization ; Vaccination ; Antibodies, Monoclonal ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Broadly Neutralizing Antibodies ; COVID-19 Vaccines ; Antibodies, Monoclonal ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adg7404
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