keyword
https://read.qxmd.com/read/38582606/pilot-scale-production-of-a-highly-efficacious-and-stable-monoglycosylated-influenza-split-virus-vaccine
#21
JOURNAL ARTICLE
Chia-Ying Wu, Shao-En Kao, Yung-Chieh Tseng, Jen-Tzu Hou, Li-Yang Wu, Juine-Ruey Chen
The yearly epidemics and unpredictable outbreaks of influenza have raisedserious concernsglobally and led to prioritizing the development of an effective vaccine toprotectagainst newly emerging variants. Previously, we demonstrated that monoglycosylated influenza virus vaccines derived from A/California/7/2009 or an updated A/Brisbane/02/2018 (IVR-190) vaccine strain recommended by WHO are superior to fully glycosylated vaccines and could broadly protect against past and new coming H1N1 variants. However, whether such a monoglycosylated virus vaccine can be mass-produced to meet clinical demands and stable enough to provide consistent efficacy against H1N1 viruses remains unclear...
April 2, 2024: Vaccine
https://read.qxmd.com/read/38580449/-the-prospect-of-biomimetic-immune-cell-membrane-coated-nanomedicines-for-treatment-of-serious-bacterial-infections-and-sepsis
#22
JOURNAL ARTICLE
Alexandria Hoffman, Victor Nizet
Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades...
April 5, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38579013/as03-adjuvant-enhances-the-magnitude-persistence-and-clonal-breadth-of-memory-b-cell-responses-to-a-plant-based-covid-19-vaccine-in-humans
#23
JOURNAL ARTICLE
Lilit Grigoryan, Yupeng Feng, Lorenza Bellusci, Lilin Lai, Bushra Wali, Madison Ellis, Meng Yuan, Prabhu S Arunachalam, Mengyun Hu, Sangeeta Kowli, Sheena Gupta, Sofia Maysel-Auslender, Holden T Maecker, Hady Samaha, Nadine Rouphael, Ian A Wilson, Alberto C Moreno, Mehul S Suthar, Surender Khurana, Stéphane Pillet, Nathalie Charland, Brian J Ward, Bali Pulendran
Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273)...
April 5, 2024: Science Immunology
https://read.qxmd.com/read/38568019/glycan-imprinted-nanoparticle-as-artificial-neutralizing-antibody-for-efficient-hiv-1-recognition-and-inhibition
#24
JOURNAL ARTICLE
Juntao Zhou, Libian Wang, Xiaoyan Liu, Yanxin Gai, Mingming Dong, Chu Wang, Muhammad Mujahid Ali, Mingliang Ye, Xianghui Yu, Lianghai Hu
The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4+ immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein...
April 3, 2024: Nano Letters
https://read.qxmd.com/read/38565882/comprehensive-landscape-of-neutralizing-antibody-and-cell-mediated-response-elicited-by-the-1-5-fractional-dose-of-17dd-yf-primary-vaccination-in-adults
#25
JOURNAL ARTICLE
Laise Rodrigues Reis, Ismael Artur Costa-Rocha, Thais Abdala-Torres, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Márcio Sobreira Silva Araújo, Elaine Spezialli, Lis Ribeiro do Valle Antonelli, Rosiane Aparecida da Silva-Pereira, Gregório Guilherme Almeida, Eder Gatti Fernandes, Francieli Fontana Sutile Tardetti Fantinato, Carla Magda Allan Santos Domingues, Maria Cristina Ferreira Lemos, Alexandre Chieppe, Jandira Aparecida Campos Lemos, Jordana Grazziela Coelho-Dos-Reis, Sheila Maria Barbosa de Lima, Adriana de Souza Azevedo, Waleska Dias Schwarcz, Luiz Antônio Bastos Camacho, Maria de Lourdes de Sousa Maia, Tatiana Guimarães de Noronha, Caroline Duault, Yael Rosenberg-Hasson, Andréa Teixeira-Carvalho, Holden Terry Maecker, Olindo Assis Martins-Filho
The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0) ] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45) ]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%...
April 2, 2024: Scientific Reports
https://read.qxmd.com/read/38562833/a-hiv-1-gp41-peptide-liposome-vaccine-elicits-neutralizing-epitope-targeted-antibody-responses-in-healthy-individuals
#26
Nathan B Erdmann, Wilton B Williams, Stephen R Walsh, Nicole Grunenberg, Paul T Edlefsen, Paul A Goepfert, Derek W Cain, Kristen W Cohen, Janine Maenza, Kenneth H Mayer, Hong Van Tieu, Magdalena E Sobieszczyk, Edith Swann, Huiyin Lu, Stephen C De Rosa, Zachary Sagawa, M Anthony Moody, Christopher B Fox, Guido Ferrari, R J Edwards, Priyamvada Acharya, S Munir Alam, Robert Parks, Margaret Barr, Georgia D Tomaras, David C Montefiori, Peter B Gilbert, M Juliana McElrath, Lawrence Corey, Barton F Haynes, Lindsey R Baden
BACKGROUND: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys. METHODS: The HVTN133 phase 1 clinical trial ( NCT03934541 ) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo...
March 18, 2024: medRxiv
https://read.qxmd.com/read/38559199/genetic-signatures-in-the-highly-virulent-subtype-b-hiv-1-conferring-immune-escape-to-v1-v2-and-v3-broadly-neutralizing-antibodies
#27
Manukumar Marichannegowda, Alonso Heredia, Yin Wang, Hongshuo Song
HIV-1 is considered to become less susceptible to existing neutralizing antibodies over time. Our study on the virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 glycan epitopes. We found that the absence of N295 and N332 glycans in the high mannose patch, which are crucial for neutralization by V3 glycan bNAbs and are typically conserved in subtype B HIV-1, is a notable feature in more than half of the VB variants...
March 13, 2024: bioRxiv
https://read.qxmd.com/read/38559180/anti-immune-complex-antibodies-are-elicited-during-repeated-immunization-with-hiv-env-immunogens
#28
Sharidan Brown, Aleksandar Antanasijevic, Leigh M Sewall, Daniel Montiel Garcia, Philip J M Brouwer, Rogier W Sanders, Andrew B Ward
UNLABELLED: Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Early antibody responses to easily accessible epitopes on these antigens are directed to non-neutralizing epitopes instead of bnAb epitopes. Autologous neutralizing antibody responses appear upon boosting once immunodominant epitopes are saturated. Here we report another type of antibody response that arises after repeated immunizations with HIV Env immunogens and present the structures of six anti-immune complexes discovered using polyclonal epitope mapping...
March 17, 2024: bioRxiv
https://read.qxmd.com/read/38559103/competitive-assembly-resolves-the-stoichiometry-of-essential-proteins-in-infectious-hiv-1-virions
#29
Haley Durden, Benjamin Preece, Rodrigo Gallegos, Ipsita Saha, Brian MacArthur, Abby Petersen, Wiley Peppel, Saveez Saffarian
UNLABELLED: During assembly on the plasma membrane, HIV-1 virions incorporate Gag-Pol as well as gp120/gp41 trimers. The Pol region consists of protease, reverse transcriptase and integrase precursors which are essential enzymes required for maturation, reverse transcription, and integration of the viral genome in the next host. gp120/gp41 trimers catalyze the fusion of the virion with its next host. Only a fraction of released virions are infectious. The stoichiometry of gp120/gp41 and Gag-Pol proteins in HIV virions was previously measured using cryotomography and ratiometric protein analysis, but what is the stoichiometry of these proteins in infectious virions remained to be determined...
March 12, 2024: bioRxiv
https://read.qxmd.com/read/38558973/protein-nanoparticle-vaccines-induce-potent-neutralizing-antibody-responses-against-mers-cov
#30
Cara W Chao, Kaitlin R Sprouse, Marcos C Miranda, Nicholas J Catanzaro, Miranda L Hubbard, Amin Addetia, Cameron Stewart, Jack T Brown, Annie Dosey, Adian Valdez, Rashmi Ravichandran, Grace G Hendricks, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Catherine Treichel, Isabelle Willoughby, Alexandra C Walls, Andrew T McGuire, Elizabeth M Leaf, Ralph S Baric, Alexandra Schäfer, David Veesler, Neil P King
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2...
March 14, 2024: bioRxiv
https://read.qxmd.com/read/38551976/modeling-resistance-to-the-broadly-neutralizing-antibody-pgt121-in-people-living-with-hiv-1
#31
JOURNAL ARTICLE
Tyler Cassidy, Kathryn E Stephenson, Dan H Barouch, Alan S Perelson
PGT121 is a broadly neutralizing antibody in clinical development for the treatment and prevention of HIV-1 infection via passive administration. PGT121 targets the HIV-1 V3-glycan and demonstrated potent antiviral activity in a phase I clinical trial. Resistance to PGT121 monotherapy rapidly occurred in the majority of participants in this trial with the sampled rebound viruses being entirely resistant to PGT121 mediated neutralization. However, two individuals experienced long-term ART-free viral suppression following antibody infusion and retained sensitivity to PGT121 upon viral rebound...
March 29, 2024: PLoS Computational Biology
https://read.qxmd.com/read/38550714/intranasal-boosting-with-rbd-hr-protein-vaccine-elicits-robust-mucosal-and-systemic-immune-responses
#32
JOURNAL ARTICLE
Li Chen, Wenyan Ren, Hong Lei, Jiayu Wang, Haiying Que, Dandan Wan, Aqu Alu, Dandan Peng, Minyang Fu, Weiqi Hong, Yuhe Huang, Xiangrong Song, Guangwen Lu, Xiawei Wei
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum, nasal lavage fluid, and bronchoalveolar lavage fluid compared with only two doses of mRNA vaccine...
July 2024: Genes & Diseases
https://read.qxmd.com/read/38548763/the-sars-cov-2-neutralizing-antibody-response-to-sd1-and-its-evasion-by-ba-2-86
#33
JOURNAL ARTICLE
Daming Zhou, Piyada Supasa, Chang Liu, Aiste Dijokaite-Guraliuc, Helen M E Duyvesteyn, Muneeswaran Selvaraj, Alexander J Mentzer, Raksha Das, Wanwisa Dejnirattisai, Nigel Temperton, Paul Klenerman, Susanna J Dunachie, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton
Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants...
March 28, 2024: Nature Communications
https://read.qxmd.com/read/38548700/immunogenicity-of-monovalent-mrna-1273-and-bnt162b2-vaccines-in-children-less-than-5-years-of-age
#34
JOURNAL ARTICLE
Trisha Dalapati, Caitlin A Williams, Elena E Giorgi, Jillian H Hurst, Savannah Herbek, Jui-Lin Chen, Christina Kosman, Alexandre T Rotta, Nicholas A Turner, Natalie Pulido, Jhoanna N Aquino, Trevor S Pfeiffer, Javier Rodriguez, Genevieve G Fouda, Sallie R Permar, Matthew S Kelly
BACKGROUND AND OBJECTIVES: The mRNA-based COVID-19 vaccines approved for use in children less than 5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to SARS-CoV-2 elicited by monovalent mRNA-based COVID-19 vaccines in young children. METHODS: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines...
March 29, 2024: Pediatrics
https://read.qxmd.com/read/38545622/hybrid-immunity-to-sars-cov-2-arises-from-serological-recall-of-igg-antibodies-distinctly-imprinted-by-infection-or-vaccination
#35
William N Voss, Michael A Mallory, Patrick O Byrne, Jeffrey M Marchioni, Sean A Knudson, John M Powers, Sarah R Leist, Bernadeta Dadonaite, Douglas R Townsend, Jessica Kain, Yimin Huang, Ed Satterwhite, Izabella N Castillo, Melissa Mattocks, Chelsea Paresi, Jennifer E Munt, Trevor Scobey, Allison Seeger, Lakshmanane Premkumar, Jesse D Bloom, George Georgiou, Jason S McLellan, Ralph S Baric, Jason J Lavinder, Gregory C Ippolito
UNLABELLED: 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...
January 23, 2024: bioRxiv
https://read.qxmd.com/read/38543852/antigen-heterologous-vaccination-regimen-triggers-alternate-antibody-targeting-in-sars-cov-2-dna-vaccinated-mice
#36
JOURNAL ARTICLE
Anders Frische, Karen Angeliki Krogfelt, Anders Fomsgaard, Ria Lassaunière
An in-depth analysis of antibody epitopes following vaccination with different regimens provides important insight for developing future vaccine strategies. B-cell epitopes conserved across virus variants may be ideal targets for vaccine-induced antibodies and therapeutic drugs. However, challenges lie in identifying these key antigenic regions, and directing the immune system to target them. We previously evaluated the immunogenicity of two candidate DNA vaccines encoding the unmodified spike protein of either the SARS-CoV-2 Index strain or the Beta variant of concern (VOC)...
February 20, 2024: Vaccines
https://read.qxmd.com/read/38543849/a-cocktail-of-lipid-nanoparticle-mrna-vaccines-broaden-immune-responses-against-%C3%AE-coronaviruses-in-a-murine-model
#37
JOURNAL ARTICLE
Yi Zhang, Jialu Zhang, Dongmei Li, Qunying Mao, Xiuling Li, Zhenglun Liang, Qian He
Severe acute respiratory syndrome (SARS)-coronavirus (CoV), Middle Eastern respiratory syndrome (MERS)-CoV, and SARS-CoV-2 have seriously threatened human life in the 21st century. Emerging and re-emerging β-coronaviruses after the coronavirus disease 2019 (COVID-19) epidemic remain possible highly pathogenic agents that can endanger human health. Thus, pan-β-coronavirus vaccine strategies to combat the upcoming dangers are urgently needed. In this study, four LNP-mRNA vaccines, named O, D, S, and M, targeting the spike protein of SARS-CoV-2 Omicron, Delta, SARS-CoV, and MERS-CoV, respectively, were synthesized and characterized for purity and integrity...
March 21, 2024: Viruses
https://read.qxmd.com/read/38543772/discordant-antigenic-properties-of-soluble-and-virion-sars-cov-2-spike-proteins
#38
JOURNAL ARTICLE
Sameer Kumar, Souradip Dasgupta, Mohammad M Sajadi, Greg A Snyder, Anthony L DeVico, Krishanu Ray
Efforts to develop vaccine and immunotherapeutic countermeasures against the COVID-19 pandemic focus on targeting the trimeric spike (S) proteins of SARS-CoV-2. Vaccines and therapeutic design strategies must impart the characteristics of virion S from historical and emerging variants onto practical constructs such as soluble, stabilized trimers. The virus spike is a heterotrimer of two subunits: S1, which includes the receptor binding domain (RBD) that binds the cell surface receptor ACE2, and S2, which mediates membrane fusion...
March 6, 2024: Viruses
https://read.qxmd.com/read/38540792/epitope-mapping-of-japanese-encephalitis-virus-neutralizing-antibodies-by-native-mass-spectrometry-and-hydrogen-deuterium-exchange
#39
JOURNAL ARTICLE
Jagat Adhikari, James Heffernan, Melissa Edeling, Estefania Fernandez, Prashant N Jethva, Michael S Diamond, Daved H Fremont, Michael L Gross
Japanese encephalitis virus (JEV) remains a global public health concern due to its epidemiological distribution and the existence of multiple strains. Neutralizing antibodies against this infection have shown efficacy in in vivo studies. Thus, elucidation of the epitopes of neutralizing antibodies can aid in the design and development of effective vaccines against different strains of JEV. Here, we describe a combination of native mass spectrometry (native-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) to complete screening of eight mouse monoclonal antibodies (MAbs) against JEV E-DIII to identify epitope regions...
March 20, 2024: Biomolecules
https://read.qxmd.com/read/38540255/broad-epitope-coverage-of-therapeutic-multi-antibody-combinations-targeting-sars-cov-2-boosts-in-vivo-protection-and-neutralization-potency-to-corner-an-immune-evading-virus
#40
JOURNAL ARTICLE
Ilse Roodink, Maartje van Erp, Andra Li, Sheila Potter, Sander M J van Duijnhoven, Milou Smits, Arthur J Kuipers, Bert Kazemier, Bob Berkeveld, Ellen van Geffen, Britte S de Vries, Danielle Rijbroek, Bianca Boers, Sanne Meurs, Wieger Hemrika, Alexandra Thom, Barry N Duplantis, Roland A Romijn, Jeremy S Houser, Jennifer L Bath, Yasmina N Abdiche
Therapeutic antibodies (Abs) which act on a broader range of epitopes may provide more durable protection against the genetic drift of a target, typical of viruses or tumors. When these Abs exist concurrently on the targeted antigen, several mechanisms of action (MoAs) can be engaged, boosting therapeutic potency. This study selected combinations of four and five Abs with non- or partially overlapping epitopes to the SARS-CoV-2 spike glycoprotein, on or outside the crucial receptor binding domain (RBD), to offer resilience to emerging variants and trigger multiple MoAs...
March 13, 2024: Biomedicines
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