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| Open AccessEpigraph hemagglutinin vaccine induces broad cross-reactive immunity against swine H3 influenza virus
A range of Influenza vaccines have been linked to induction of adaptive immunity in a number of animal models. Here, the authors utilize a computational design strategy and produce a swine H3 influenza vaccine which shows enhanced efficacy in both murine and porcine infectious disease models.
- Brianna L. Bullard
- , Brigette N. Corder
- & Eric A. Weaver
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| Open AccessA tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans
Multivalent vaccines that confer protection to multiple serotypes of Dengue virus have been established. Here the authors examine the presence of vaccine induced multivalent antibodies and how these link to protection in a human challenge model of Dengue virus.
- Usha K. Nivarthi
- , Jesica Swanstrom
- & Aravinda M. de Silva
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| Open AccessA single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2
Several mRNA-based vaccines for SARS-CoV-2 are in late phase clinical development. Here, the authors show that a single immunization with a mRNA vaccine expressing SARS-CoV-2 spike RBD induces neutralizing antibodies that are maintained for at least 6.5 months and confer protection in a sera transfer study in mice.
- Qingrui Huang
- , Kai Ji
- & Jinghua Yan
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| Open AccessA COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses
Vaccines for SARS-COV-2 are needed in the ongoing pandemic. Here the authors characterize a vaccine candidate that presents the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on a synthetic VLP platform using SpyTag/SpyCatcher technology and show immunogenicity of a prime-boost regimen in mice and pigs.
- Tiong Kit Tan
- , Pramila Rijal
- & Alain R. Townsend
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| Open AccessModelling the global burden of drug-resistant tuberculosis avertable by a post-exposure vaccine
Vaccines preventing tuberculosis disease progression have shown promising results in recent trials. Here, the authors use mathematical modelling to estimate that this type of vaccine could avert 10% of cases of rifampicin-resistant tuberculosis and 7% of deaths from 2020-2035.
- Han Fu
- , Joseph A. Lewnard
- & Nimalan Arinaminpathy
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Article
| Open AccessSARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice
Here, the authors characterize a SARS-CoV-2 subunit vaccine candidate that contains full-length spike protein stabilized in its prefusion conformation, and show immunogenicity in baboons and protection in mice with Matrix-M adjuvanted vaccine.
- Jing-Hui Tian
- , Nita Patel
- & Gale Smith
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| Open AccessCharacterization of a new Leishmania major strain for use in a controlled human infection model
Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development. Here, the authors describe the isolation, characterization, and GMP manufacture of a clinical Leishmania major strain to be used as a resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.
- Helen Ashwin
- , Jovana Sadlova
- & Paul M. Kaye
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Article
| Open AccessStabilizing the closed SARS-CoV-2 spike trimer
SARS-CoV-2 S protein prematurely refolds to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yield. Here, Juraszek et al. present a stable SARS-CoV-2 S-closed protein variant with increased expression and correct folding, predominantly in closed prefusion conformation.
- Jarek Juraszek
- , Lucy Rutten
- & Johannes P. M. Langedijk
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| Open AccessA single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge
Here, the authors generate a replication-competent VSV based vaccine expressing SARS-CoV-2 spike protein and show protection in the hamster model with one dose. Analysis of the antibody response in mice shows induction of neutralizing antibodies and suggests a desirable Th1-biased response to the vaccine.
- Yfat Yahalom-Ronen
- , Hadas Tamir
- & Tomer Israely
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| Open AccessDevelopment of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform
Chiuppesi et al. demonstrate the use of a synthetic poxvirus-based platform to rapidly generate multi-antigenic vaccine candidates expressing spike and nucleocapsid antigens of SARS-CoV-2. Immunization of mice stimulates potent antigen-specific humoral and cellular immune responses, including neutralizing antibodies.
- Flavia Chiuppesi
- , Marcela d’Alincourt Salazar
- & Felix Wussow
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Article
| Open AccessEpidemiology and biology of a herpesvirus in rabies endemic vampire bat populations
Here, Griffiths et al. show infection of 80–100% of sampled vampire bats in Peru with a newly discovered betaherpesvirus (DrBHV) that exhibits specificity within neotropical bats and evidence for superinfection. These data suggest that DrBHV could be a candidate for virally vectored vaccines that spread autonomously through a bat population.
- Megan E. Griffiths
- , Laura M. Bergner
- & Daniel G. Streicker
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| Open AccessVaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells
A vaccine to generate durable HIV broadly neutralizing antibodies (bnAb) from engineered B cells holds promise as an HIV functional cure. Here, the authors show that CRISPR/Cas-modified B cells expressing bnAbs as functional antigen receptors can be immunized to generate long-lived, germinal centre matured bnAb memory and plasma cells in mice.
- Deli Huang
- , Jenny Tuyet Tran
- & James E. Voss
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Article
| Open AccessTh17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients
The folate receptor alpha (FRα) is overexpressed in the majority of high-grade serous ovarian cancers and has been proposed as a candidate vaccine antigen. Here the authors report the safety and immunogenicity of Th17-inducing dendritic cells pulsed with FRα-derived epitopes in an early phase I clinical trial with ovarian cancer patients.
- Matthew S. Block
- , Allan B. Dietz
- & Martin J. Cannon
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Article
| Open AccessImmunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity
4CMenB is an approved multi-component vaccine against Serogroup B meningococcus. Here the authors develop a protein microarray for three major 4CMenB antigenic components (fHbp, NHBA and NadA) and describe antibody repertoires in sera from vaccinated infants, adolescents and adults correlating with bactericidal response.
- E. Bartolini
- , E. Borgogni
- & D. Maione
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Article
| Open AccessStructural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A
Neisseria meningitidis capsular polysaccharide (CPS) is a major virulence factor and vaccine formulations against Neisseria meningitidis serogroup A (NmA) contain O-acetylated CPS. Here, the authors provide mechanistic insights into CPS O-acetylation in NmA by determining the crystal structure of the O-acetyltransferase CsaC and NMR measurements further reveal that the CsaC-mediated reaction is regioselective for O3 and that the O4 modification results from spontaneous O-acetyl migration.
- Timm Fiebig
- , Johannes T. Cramer
- & Martina Mühlenhoff
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Article
| Open AccessEnhancing mucosal immunity by transient microbiota depletion
Tissue resident CD8 + T cells present at mucosal surfaces are poised to elicit function in situ, however approaches to boost their number in the gastrointestinal mucosa has been limited. Here the authors combine the use of Listeria monocytogenese and transient depletion of the intestinal microbiome to boost the resident CD8 + T cell response.
- Simone Becattini
- , Eric R. Littmann
- & Eric G. Pamer
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| Open AccessA stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A
The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.
- Jacopo Enotarpi
- , Marta Tontini
- & Roberto Adamo
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| Open AccessRepertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction
Identifying peptides that can bind major histocompatibility complex II (MHC-II) is important for our understanding of T cell immunity and specificity. Here the authors present a yeast-display library screening approach that identifies more potential binders than various reported algorithms to help expand our understanding for antigen presentation.
- C. Garrett Rappazzo
- , Brooke D. Huisman
- & Michael E. Birnbaum
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| Open AccessAn adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques
A vaccine protecting from SARS-CoV-2 infection is needed. Here the authors generate a replication-incompetent adenovirus based vaccine expressing SARS-CoV-2 spike, show protection from infection in non-human primates, and analyze the immune response after intramuscular and intranasal vaccination.
- Liqiang Feng
- , Qian Wang
- & Ling Chen
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Article
| Open AccessA single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge
A vaccine preventing infection and transmission of SARS-CoV-2 is needed. Here, Wu et al. generate an adenovirus-vector vaccine expressing SARS-CoV-2 spike protein and show that a single dose of mucosal vaccination protects mice and ferrets from infection and inhibits virus replication in the upper respiratory tract.
- Shipo Wu
- , Gongxun Zhong
- & Wei Chen
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Article
| Open AccessQuantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans
The authors provide a comprehensive characterization of the human antibody response to a licensed hepatitis E virus (HEV) vaccine, Hecolin, in four individuals over the course of six months post vaccination. They demonstrate diverse patterns of antibody response underlying the vaccine protection.
- Gui-Ping Wen
- , Linling He
- & Ning-Shao Xia
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Article
| Open AccessPrior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment
During an ongoing Ebola virus outbreak, infection before onset of protective immunity from vaccination is a possible scenario. Here the authors show in non-human primates that vaccination shortly before treatment with a monoclonal antibody does not negatively affect effectiveness of the antibody therapy.
- Robert W. Cross
- , Zachary A. Bornholdt
- & Thomas W. Geisbert
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| Open AccessCross-serotype protection against group A Streptococcal infections induced by immunization with SPy_2191
A high number of serotypes makes vaccine development to group A Streptococcus (GAS) difficult. Here, the authors use a reverse vaccinology approach and identify SPy_2191 as conserved surface protein that inhibits GAS adhesion and invasion and induces cross-protective immunity in mice.
- Pooja Sanduja
- , Manish Gupta
- & Atul Kumar Johri
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| Open AccessA second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing
Here, the authors engineer an attenuated knock-out Leishmania (LmCen−/−) vaccine that is safe in immunocompromised mice and induces an immune response and protection similar to leishmanization with wild-type Leishmania. Since LmCen−/− is antibiotic resistant marker free, it is a candidate for clinical development.
- Wen-Wei Zhang
- , Subir Karmakar
- & Hira L. Nakhasi
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Article
| Open AccessSelf-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice
Here, the authors develop a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine candidate and show induction of neutralization antibody titers in mice that are comparable to titers in convalescent sera of patients.
- Paul F. McKay
- , Kai Hu
- & Robin J. Shattock
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Article
| Open AccessDurable protection against repeated penile exposures to simian-human immunodeficiency virus by broadly neutralizing antibodies
Here, using a repeat-exposure penile SHIV infection model in macaques, the authors show that a single subcutaneous administration of a broadly neutralizing antibody (bNAb) exerts long-acting protection against both penile and vaginal virus exposure, which highlights bNAbs as a potential therapeutic for LA-PrEP.
- David A. Garber
- , Debra R. Adams
- & Walid Heneine
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| Open AccessRational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles
An effective vaccine for human papillomavirus (HPV) needs to protect from several genotypes. Here, Wang et al. provide a strategy to produce single capsomere-hybrid virus-like particle (chVLP) composed of capsomers of different genotypes and show that a nona-type chVLP induces similar levels of neutralizing antibodies as an approved HPV vaccine.
- Daning Wang
- , Xinlin Liu
- & Shaowei Li
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Article
| Open AccessImmunogenicity of a DNA vaccine candidate for COVID-19
There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.
- Trevor R. F. Smith
- , Ami Patel
- & Kate E. Broderick
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Article
| Open AccessThe CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice
Senotherapy, the removal of aged T cells, is an effective approach to attenuate age-related diseases. Here the authors report a CD153 targeting vaccine that prevents the accumulation of senescent adipose tissue T cells in mice on high-fat diet, which is associated with improved glucose tolerance.
- Shota Yoshida
- , Hironori Nakagami
- & Hiromi Rakugi
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| Open AccessAntigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine
Vaccine mismatch and changes in antigenicity due to vaccine strain egg adaptation can affect seasonal influenza vaccine effectiveness. Here, Gouma et al. show that the egg-adapted 3c3.A H3N2 vaccine strain elicits antibodies with limited reactivity to a wildtype 3c3.A strain and currently circulating 3c2.A H3N2 strains.
- Sigrid Gouma
- , Madison Weirick
- & Scott E. Hensley
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| Open AccessHigh residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi
Impact of pneumococcal conjugate vaccines (PCV) in controlling carriage needs to be evaluated to inform vaccine policy. Here, Swarthout et al. show in a prospective rolling cross-sectional study in Malawi a high residual prevalence of vaccine-serotype S. pneumoniae 7 years after PCV introduction.
- Todd D. Swarthout
- , Claudio Fronterre
- & Robert S. Heyderman
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Article
| Open AccessImmune checkpoint modulation enhances HIV-1 antibody induction
Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.
- Todd Bradley
- , Masayuki Kuraoka
- & Barton F. Haynes
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| Open AccessOuter membrane protein size and LPS O-antigen define protective antibody targeting to the Salmonella surface
The O-antigen of LPS is known to limit the binding of antibody to bacterial surface antigens. Here the AUs show that the chemical and physical structure of the O-antigen are central factors in limiting the exposure of surface antigens to antibodies during Salmonella infection, thus defining their protective qualities.
- C. Coral Domínguez-Medina
- , Marisol Pérez-Toledo
- & Adam F. Cunningham
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Article
| Open AccessGlycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses
Influenza virus hemagglutinin (HA) stem between group 1 and 2 viruses has different glycosylation patterns, likely hampering cross-group protection. Here, Boyoglu-Barnum et al. show that introducing a group 2 glycan into a group 1 stem nanoparticle vaccine broadens antibody responses in mice to cross-react with group 2 HAs.
- Seyhan Boyoglu-Barnum
- , Geoffrey B. Hutchinson
- & Masaru Kanekiyo
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Article
| Open AccessDisruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements
Here, using cryo-EM and smFRET, Henderson et al. show how tryptophan 571 in the HIV-1 Env acts as a conformational switch during receptor-mediated viral entry and design HIV-1 Env proteins that cannot undergo conformational changes. This has important implications for HIV-1 vaccine design.
- Rory Henderson
- , Maolin Lu
- & S. Munir Alam
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Article
| Open AccessOil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis
Here, the authors meta-analyze clinical trials comparing adjuvanted and non-adjuvanted influenza vaccines in children and find that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy immunologically naive children.
- Yu-Ju Lin
- , Chiao-Ni Wen
- & Chi-Tai Fang
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Article
| Open AccessMaternal vaccination and protective immunity against Zika virus vertical transmission
A Zika virus vaccine should protect the fetus during pregnancy. Here, using a live-attenuated Zika vaccine, the authors show that a higher neutralizing antibody titer is required to protect from in utero transmission than to protect non-pregnant mice and that a single maternal immunization protects the fetus from infection and disease.
- Chao Shan
- , Xuping Xie
- & Pei-Yong Shi
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Article
| Open AccessBridging the gap between efficacy trials and model-based impact evaluation for new tuberculosis vaccines
One measurement of tuberculosis vaccine efficacy in clinical trials is prevention of disease, but different mechanisms can underlie disease prevention. Here, the authors develop a mathematical model that allows to identify mechanisms of action of a vaccine preventing TB disease.
- Mario Tovar
- , Sergio Arregui
- & Yamir Moreno
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Article
| Open AccessAn MPER antibody neutralizes HIV-1 using germline features shared among donors
Here, the authors identify a broadly neutralizing antibody from an HIV-infected person that recognizes the membrane-proximal external region (MPER) of HIV envelope glycoprotein (Env) and has a short CDRH3 and low polyreactivity. Structural analysis shows how the antibody binds the MPER and Env on the viral membrane.
- Lei Zhang
- , Adriana Irimia
- & Michael B. Zwick
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Article
| Open AccessAn inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases
Successful anticancer immunotherapy should induce robust systemic immunity against metastases. Here, the authors engineer an inhalable nano-STING agonist, which synergizes with fractionated radiation to control lung metastases and confers long-term systemic antitumor immunity in mice.
- Yang Liu
- , William N. Crowe
- & Dawen Zhao
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Article
| Open AccessOligomeric state of the ZIKV E protein defines protective immune responses
Many human antibodies that neutralize Zika virus recognize quaternary epitopes on the envelope (E) protein. Here, Metz et al. engineer stable recombinant homodimers of Zika virus E protein and show that it induces neutralizing antibodies in mice that recognize similar epitopes as human antibodies from Zika infected people.
- Stefan W. Metz
- , Ashlie Thomas
- & Aravinda M. de Silva
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Article
| Open AccessViral N6-methyladenosine upregulates replication and pathogenesis of human respiratory syncytial virus
Here, Xue et al. identify N6-methyladenosine (m6A) modification sites in RNAs of respiratory syncytial virus (RSV) and show that these sites, particularly sites in the transcript encoding for the viral glycoprotein, affect virus replication in primary human cells and cotton rats.
- Miaoge Xue
- , Boxuan Simen Zhao
- & Jianrong Li
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Article
| Open AccessPotent antibody lineage against malaria transmission elicited by human vaccination with Pfs25
Pfs25 is a transmission-blocking vaccine candidate for Plasmodium. Here, McLeod et al. analyze the antibody response to Pfs25 in sera from a clinical trial evaluating a Pfs25 vaccine candidate, identify a potent transmission-blocking antibody and determine recognized epitopes on Pfs25.
- Brandon McLeod
- , Kazutoyo Miura
- & Jean-Philippe Julien
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Article
| Open AccessEnhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle
Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.
- Philip J. M. Brouwer
- , Aleksandar Antanasijevic
- & Rogier W. Sanders
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Article
| Open AccessInnate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites
Here, Minkah et al. show that, while immunization with replication-competent Plasmodium parasites can confer sterile protection against infection, it also induces a type I interferon response that adversely affects anti-malaria immunity by affecting numbers of protective hepatic CD8 T cells and CD8 T cell function.
- Nana K. Minkah
- , Brandon K. Wilder
- & Stefan H. I. Kappe
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Article
| Open AccessExposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies
Antibody cross-reactivity can help to prevent escape mutations from enabling viral escape, but underlying mechanisms are unclear. Here the authors identify influenza hemagglutinin epitopes that are exposed during viral replication and which result in the generation of a class of protective cross-reactive antibodies.
- Yu Adachi
- , Keisuke Tonouchi
- & Yoshimasa Takahashi
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Article
| Open AccessZIKV infection induces robust Th1-like Tfh cell and long-term protective antibody responses in immunocompetent mice
Here, the authors show that Zika virus (ZIKV) infection induces Th1-like Tfh cells that depend on T-bet for their development and are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses.
- Huabin Liang
- , Jinyi Tang
- & Haikun Wang
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Article
| Open AccessDevelopment of a SFTSV DNA vaccine that confers complete protection against lethal infection in ferrets
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus with no specific treatment or vaccine available. Here, the authors develop a DNA vaccine for SFTSV that is protective against lethal challenge in ferrets and show that anti-envelope antibodies are important for protection.
- Jeong-Eun Kwak
- , Young-Il Kim
- & Su-Hyung Park
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Article
| Open AccessDissecting the heterogeneity of DENV vaccine-elicited cellular immunity using single-cell RNA sequencing and metabolic profiling
Using a combination of single-cell RNA sequencing and TCR clonotype analysis on longitudinal samples from dengue vaccinated individuals, Waickman et al. here define a transcriptional signature in acutely-activated T cells that is associated with durable CD8+ T cell memory.
- Adam T. Waickman
- , Kaitlin Victor
- & Jeffrey R. Currier