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| Open AccessHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it’s specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.
- Shixia Wang
- , Kun-Wei Chan
- & Shan Lu
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Article
| Open AccessOriginal COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters
Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.
- Luca M. Zaeck
- , Ngoc H. Tan
- & Rory D. de Vries
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| Open AccessRecruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow
The mechanisms driving B cell differentiation into resident bone marrow plasma cells (BMPC) remain unclear. Here the authors use single cell sequencing and BMPC phenotyping to infer developmental pathways and regulation by IL-21 in germinal centres to promote maintenance of BMPC after vaccination in humans.
- Marta Ferreira-Gomes
- , Yidan Chen
- & Mir-Farzin Mashreghi
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| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
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| Open AccessPredicting vaccine effectiveness for mpox
Here, based on a systematic review and meta-analysis, the authors analyze the relationship between vaccine immunogenicity and vaccine protection against mpox and predict the durability of protection after vaccination. This helps inform the optimal vaccine deployment in a health emergency.
- Matthew T. Berry
- , Shanchita R. Khan
- & David S. Khoury
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| Open AccessAdjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus
Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.
- Jacob A. Dillard
- , Sharon A. Taft-Benz
- & Mark T. Heise
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| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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| Open AccessA comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus
Poly-β-(1–6)-N-acetylglucosamine (PNAG) is an important vaccine target, but the impact of the number and position of free amine vs N-acetylation on its antigenicity is not well understood. Here, the authors report a divergent strategy to synthesize a comprehensive library of PNAG pentasaccharides, enabling the identification of enhanced epitopes for vaccines against Staphylococcus aureus including drug resistant strains.
- Zibin Tan
- , Weizhun Yang
- & Xuefei Huang
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Article
| Open AccessMulti-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
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Article
| Open AccessAn ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation
Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.
- Seoryeong Park
- , Jaewon Choi
- & Junho Chung
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Article
| Open AccessInfluenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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| Open AccessCoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits
HIV vaccine candidates often have limited capacity to induce broadly neutralizing antibodies (nAbs). In this study, the authors show that stabilized Clade C HIV-1 Env protein trimers decorated on CoPoP liposomes induce nAbs against 18 of 20 multiclade tier 2 HIV-1 strains in immunized rabbits.
- Annemart Koornneef
- , Kanika Vanshylla
- & Frank Wegmann
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| Open AccessVaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin
Immune imprinting can affect the response to future infection with pathogen variants. Here, Pušnik et. al. demonstrate that previous vaccination with wild-type SARS-CoV-2 vaccine hampers the formation of an immune response to mutated regions of omicron surface proteins following omicron breakthrough infection.
- Jernej Pušnik
- , Jasmin Zorn
- & Hendrik Streeck
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| Open AccessSARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals
Prior infection or exposure to SARS-CoV-2 may influence immunogenicity and effectiveness of subsequent vaccination to new strains of virus. Here the authors show that immunogenicity of a BA.4/5 mRNA vaccine differed in recipients depending on whether they had been exposed to or infected with an earlier strain of virus.
- Rebecca Urschel
- , Saskia Bronder
- & Martina Sester
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Article
| Open AccessA live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections
Authors utilise a murine model of Escherichia coli infection to immunologically characterise the properties of their live attenuated vaccine candidate. They also demonstrate protection of newborn mice following maternal immunisation.
- Youssouf Sereme
- , Cécile Schrimp
- & David Skurnik
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| Open AccessImmunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients
SARS-CoV-2 immune responses after vaccination in individuals with multiple sclerosis (MS) remain poorly understood. Here, using mass cytometry, the authors demonstrate that, following three doses of mRNA vaccine, patients with MS have distinct metabolic profiles in antigen-specific B and T cells.
- Sara De Biasi
- , Domenico Lo Tartaro
- & Andrea Cossarizza
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Article
| Open AccessMultipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial
Peptide-based cancer vaccines require epitopes for both CD8+ and CD4+ T cells. Here the authors report the long-term outcomes of a randomized phase II trial (NCT00118274) in patients with melanoma designed to evaluate a class I MHC-restricted peptide vaccine plus one of two “helper” peptide preparations to stimulate CD4+ T cells, either non-specific help or melanoma-specific help.
- Emily K. Ninmer
- , Hong Zhu
- & Craig L. Slingluff Jr
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| Open AccessPredictive evolutionary modelling for influenza virus by site-based dynamics of mutations
Seasonal influenza vaccine effectiveness depends on including virus strains in the vaccine that closely match those circulating in the upcoming season. In this study, the authors develop a computational model of influenza virus evolution to predict future circulating strains and therefore support vaccine strain selection.
- Jingzhi Lou
- , Weiwen Liang
- & Maggie Haitian Wang
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| Open AccessImmunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
In this study, the authors report a mutation that increases the production of recombinant SARS-CoV-2 Spike and exposure of the RBD. In animal models, a Spike-based vaccine containing the mutation induces strong immunogenicity, provides protection from disease and results in faster tissue viral clearance.
- Carlos Ávila-Nieto
- , Júlia Vergara-Alert
- & Jorge Carrillo
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| Open AccessEngineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages
Here the authors describe a stabilization technology that engineers crosslinks between tyrosine sidechains into a natively folded vaccine immunogen and show that immunogenicity is improved in small animal models by locking the most potently neutralizing epitopes.
- Sonal V. Gidwani
- , Devarshi Brahmbhatt
- & Mark A. Yondola
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| Open AccessQuantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.
- Craig A. Magaret
- , Li Li
- & Peter B. Gilbert
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| Open AccessImpact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study
SARS-CoV-2 infection is associated with an increased risk of arterial and venous thrombotic events. Here, the authors investigate the degree to which this association is modified by virus variant and vaccination using electronic health record data for ~18 million adults in England.
- Genevieve I. Cezard
- , Rachel E. Denholm
- & Venexia Walker
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| Open AccessAntiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis
Epidemics of whooping cough caused by Bordetella pertussis have been seen and are linked to waning immunity globally. Here the authors explore responses to inactivated poliovirus (IPV) in the Tdap-IPV vaccine and show it stimulates early antiviral responses in monocytes and dendritic cells that are associated with long-lived pertussis antibody responses.
- Joshua Gillard
- , Madeleine Suffiotti
- & Dimitri A. Diavatopoulos
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| Open AccessMalaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin
Blood and liver stages of malaria parasites can affect each other, but it’s not clear how this may affect live-attenuated whole parasite vaccination. Here the authors show that malaria parasite blood stage infection subdues new infection and vaccination by suppressing growth of its liver stage via host cytokines.
- Hardik Patel
- , Nana K. Minkah
- & Stefan H. I. Kappe
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| Open AccessComparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States
The optimal frequency of COVID-19 booster vaccination is unclear. Here, the authors use a microsimulation model to assess the impact of different vaccine schedules on severe disease and show that regular boosters have large benefits for older and immunocompromised individuals but less so for younger age groups.
- Hailey J. Park
- , Gregg S. Gonsalves
- & Nathan C. Lo
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Article
| Open AccessQ586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids
Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.
- Benoit Stijlemans
- , Patrick De Baetselier
- & Carl De Trez
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| Open AccessPrior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection
Flavivirus infection or vaccination can induce cross-reactive immune responses. Here, the authors show how previous immunization with the tick-borne encephalitis virus vaccine affects the immune response to the yellow fever vaccine, suggesting that the yellow fever vaccine virus conceals epitopes shared with other flaviviruses in flavivirus-naive but not flavivirus-pre-exposed individuals.
- Antonio Santos-Peral
- , Fabian Luppa
- & Simon Rothenfusser
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| Open AccessPrefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
Broadly protective vaccines are needed to combat current and future human coronaviruses. Here the authors use structure-based design to engineer spike S2-only antigens that provide partial protection from sarbecovirus challenge in mice.
- Ching-Lin Hsieh
- , Sarah R. Leist
- & Jason S. McLellan
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| Open AccessA general computational design strategy for stabilizing viral class I fusion proteins
The authors present a generalisable computational approach to stabilize class I fusion proteins in the prefusion state. The method was used to stabilize the fusion proteins of RSV, hMPV, and SARS-CoV-2 viruses, with the designs structurally validated and RSV F protein assessed in a neutralization assay.
- Karen J. Gonzalez
- , Jiachen Huang
- & Eva-Maria Strauch
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| Open AccessApplying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins
Here the authors develop a DNA vaccine, mixing 18 hemagglutinin (HA) subtypes monovalently into heterodimeric molecules, and show that it induces broadly reactive antibodies against subdominant HA epitopes and heterologous protection against influenza A viruses in mice.
- Daniëla Maria Hinke
- , Ane Marie Anderson
- & Ranveig Braathen
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| Open AccessBroad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine
Evolution of SARS-CoV-2 and emergence of other sarbecoviruses are of potential concern. Here, the authors designed a trivalent spike-protein-nanoparticle vaccine that elicits neutralizing antibodies and protects female hamsters against challenges with SARS-CoV-2-like and SARS-CoV-1-like coronaviruses.
- Peter J. Halfmann
- , Kathryn Loeffler
- & Ravi S. Kane
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| Open AccessMAIVeSS: streamlined selection of antigenically matched, high-yield viruses for seasonal influenza vaccine production
Vaccines combat global influenza threats, relying on timely selection of optimal seed viruses. Here, authors introduce MAIVeSS, a machine learning assisted framework to streamline vaccine seed virus selection using genomic sequence, expediting seasonal flu vaccine production and supply.
- Cheng Gao
- , Feng Wen
- & Xiu-Feng Wan
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Article
| Open AccessAn intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission
In this study, the authors evaluated the protective capacity of a mucosal, live-attenuated SARS-CoV-2 vaccine and show that it induces systemic and mucosal humoral immunity, protects from clinical disease symptoms, and prevents virus transmission in hamsters more efficiently than an intramuscular mRNA vaccine.
- Julia M. Adler
- , Ricardo Martin Vidal
- & Jakob Trimpert
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| Open AccessA Gamma-adapted subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants and protects mice from infection
Here the authors show that a Gamma-based subunit vaccine induces broadly neutralizing antibodies against SARS-CoV-2 variants including Omicron, induces cellular immune responses, and protects mice from infection with Omicron BA.5 SARS-CoV-2.
- Lorena M. Coria
- , Juan Manuel Rodriguez
- & Juliana Cassataro
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Article
| Open AccessMaternal pertussis immunization and the blunting of routine vaccine effectiveness: a meta-analysis and modeling study
Pertussis immunisation for pregnant women has been introduced to protect newborns, but immunological evidence suggests that this lessens subsequent infant immune response to vaccination. Here, the authors assess the epidemiological impacts of both consequences of maternal immunisation on infant infection.
- Michael Briga
- , Elizabeth Goult
- & Matthieu Domenech de Cellès
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| Open AccessEnhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds
Three-dimensional DNA origami constructs can be used to deliver vaccine antigens in a multi-valent form. Here the authors design a DNA origami system for SARS-CoV-2 proteins and characterize in mice the immune response and protective capacity of generated antibodies, finding that the construct itself is not immunogenic.
- Eike-Christian Wamhoff
- , Larance Ronsard
- & Mark Bathe
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Article
| Open AccessHumoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination
Nziza et al. profile anti-SARS-CoV-2 antibody responses in infants and toddlers after mRNA vaccination and demonstrate a strong functional activation of humoral immunity in this age group when compared with adults and naturally infected children.
- Nadège Nziza
- , Yixiang Deng
- & Lael M. Yonker
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Article
| Open AccessNon-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines
Different approaches have been described for the transdermal delivery of drugs. Here the authors report the design of a fluorocarbon modified chitosan-based non-invasive transdermal platform for the delivery of biomacromolecules, such as viral antigens for vaccines or immune checkpoint inhibitors for melanoma immunotherapy.
- Wenjun Zhu
- , Ting Wei
- & Zhuang Liu
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Article
| Open AccessNanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models
Here the authors screen different lipid nanoparticle (LNP) formulations for intramuscular delivery of plasmid DNA and uptake by antigen-presenting cells. The lead LNP exhibits immunogenicity and protection in small animal models that is comparable to approved SARS-CoV-2 mRNA vaccine formulations.
- Lays Cordeiro Guimaraes
- , Pedro Augusto Carvalho Costa
- & Pedro Pires Goulart Guimaraes
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Article
| Open AccessCleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability
Gorman et al. designed a Lassa virus prefusion-stabilized soluble glycoprotein complex trimer (GPC), with which they identified a Lassa virus-neutralizing nanobody that bound the GPC apex and elicited neutralizing antibody responses in guinea pigs.
- Jason Gorman
- , Crystal Sao-Fong Cheung
- & Peter D. Kwong
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Article
| Open AccessRedirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines
Here the authors report an exploratory analysis of a clinical trial that tested different influenza virus vaccination platforms. The results show that multiple seasons of recombinant or cell-based influenza vaccinations may be needed to redirect antibody responses away from immune memory to egg-adapted epitopes and refocus on epitopes on the circulating viruses.
- Feng Liu
- , F. Liaini Gross
- & Min Z. Levine
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Article
| Open AccessDynamic predictors of COVID-19 vaccination uptake and their interconnections over two years in Hong Kong
Understanding factors associated with COVID-19 vaccine uptake in an evolving pandemic context is important for future vaccine campaigns. Here, the authors investigate the main drivers of vaccine hesitancy in Hong Kong at different stages of the pandemic, where uptake was initially low despite high availability.
- Jiehu Yuan
- , Yucan Xu
- & Qiuyan Liao
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Article
| Open AccessDiverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques
An adjuvanted SARS-CoV-2 spike-ferritin nanoparticle vaccine can elicit antibodies with relatively broad sarbecovirus activity in non-human primates. Here, the authors isolate and structurally characterize several monoclonal antibodies providing insights into the targeted epitopes and broad reactivity.
- Rajeshwer S. Sankhala
- , Kerri G. Lal
- & M. Gordon Joyce
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Article
| Open AccessMucosal TLR5 activation controls healthspan and longevity
Understanding how the immune system’s functionality declines with age is crucial for addressing aging-related health issues. Here, the authors demonstrate that activating TLR5 in the mucosal layer can significantly improve healthspan and longevity, suggesting a novel approach for aging interventions.
- Jae Sung Lim
- , Eun Jae Jeon
- & Kyung A Cho
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Article
| Open AccessT-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
CD3 bispecific antibodies (bsAbs) have demonstrated promising clinical responses in hematological malignancies but clinical benefit in solid tumors has been limited. Here the authors report that pre-treatment vaccination promotes the infiltration of tumor-(un)related effector CD8 T cells, improving the efficacy of CD3 bsAbs in solid tumors.
- Jim Middelburg
- , Marjolein Sluijter
- & Thorbald van Hall
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Article
| Open AccessBCG vaccination-induced acquired control of mycobacterial growth differs from growth control preexisting to BCG vaccination
Bacillus Calmette-Guèrin vaccination prevents tuberculosis but some individuals control infection without immunization. Here the authors employ functional assessment of effector responses against mycobacteria to find that distinct gene expression profiles for pre-existing capacity to control and control induced by BCG vaccination.
- Krista E. van Meijgaarden
- , Wenchao Li
- & Simone A. Joosten
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Article
| Open AccessDistinct gene expression signatures comparing latent tuberculosis infection with different routes of Bacillus Calmette-Guérin vaccination
The ability of BCG vaccination to prevent pulmonary tuberculosis could be improved by targeting mucosal immunity within the lung. Here the authors compare latent Mtb-infected donors with intradermal or oral BCG vaccine recipients to show distinct systemic and pulmonary immune responses are induced by differing routes of natural infection or vaccination.
- Richard F. Silver
- , Mei Xia
- & Daniel F. Hoft
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Article
| Open AccessQuantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection
Modified vaccinia Ankara (MVA) virus is the vaccine deployed to curb mpox. Here the authors conduct a multiplexed proteomic analysis to quantify cellular and viral proteins throughout MVA virus infection of human fibroblasts and macrophages and see substantial remodelling of the host proteome.
- Jonas D. Albarnaz
- , Joanne Kite
- & Michael P. Weekes
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Article
| Open AccessEarly mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine
Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses.
- Ryan S. Thwaites
- , Ashley S. S. Uruchurtu
- & Peter J. M. Openshaw