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| Open AccessUniversal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.
- Johannes P. M. Langedijk
- , Freek Cox
- & Mark J. G. Bakkers
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Article
| 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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Article
| 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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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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Article
| 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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Article
| 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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Article
| 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 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 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 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 AccessEngineered immunogens to elicit antibodies against conserved coronavirus epitopes
A pan-betacoronavirus vaccine will likely require the elicitation of antibodies against spike regions conserved across diverse coronaviruses. Here, authors computationally engineer and experimentally validate immunogens to elicit antibodies against two such spike regions.
- A. Brenda Kapingidza
- , Daniel J. Marston
- & Mihai L. Azoitei
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Article
| Open AccessAn FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission
Here the authors develop a mucosal SARS-CoV-2 vaccine and show immunogenicity and protection in mice as well as reduced virus transmission in hamsters. This protein vaccine consists of a stabilized spike protein fused to monomeric IgG Fc, supporting its transport across epithelial barriers by binding to the neonatal Fc receptor.
- Weizhong Li
- , Tao Wang
- & Xiaoping Zhu
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Article
| Open AccessNanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera
Most current anti-coronavirus nanoparticle vaccines target epitopes within the RBD. Here, the authors developed nanoparticles displaying an array of spike fusion proteins derived from various coronaviruses and show that immunizing mice with these vaccines elicits broad and potent cross-reactive antibodies.
- Geoffrey B. Hutchinson
- , Olubukola M. Abiona
- & Kizzmekia S. Corbett-Helaire
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Article
| Open AccessStructure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies
The AMA1-RON2 complex is important for Plasmodium falciparum invasion and a potential vaccine target. Here the authors engineer a fusion protein of AMA1 and RON2 loop that mimics the receptor-ligand complex and show that it induces antibodies that neutralize non-vaccine type parasites.
- Sean Yanik
- , Varsha Venkatesh
- & Prakash Srinivasan
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Article
| Open AccessStructure-based design of a strain transcending AMA1-RON2L malaria vaccine
Here the authors use structure-based design to engineer a single component immunogen that mimics the malaria parasite AMA1-RON2 complex required for invasion of host cells, and show that it elicits a potent strain-transcending antibody response in rats.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
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Article
| Open AccessAntibody-mediated NK cell activation as a correlate of immunity against influenza infection
Antibodies play a crucial role in protection from influenza virus infection, but functional details, particularly in older adults, are incomplete. Here the authors show that NK cell-activating antibodies are associated with protection from influenza infection in vaccinated older adults.
- Carolyn M. Boudreau
- , John S. Burke IV
- & Galit Alter
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Article
| Open AccessLymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice
There is a clinical need for effective and efficacious vaccines for Epstein-Barr virus (EBV) that induce substantive and protective immunity. Here the authors use a combined lymph-node targeted adjuvant and subunit vaccine against EBV and show the induction and effectiveness in a human leukocyte antigen expressing murine model.’
- Vijayendra Dasari
- , Lisa K. McNeil
- & Rajiv Khanna
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| Open AccessSafety and immunogenicity of a SARS-CoV-2 Gamma variant RBD-based protein adjuvanted vaccine used as booster in healthy adults
Here the authors show in a phase 1 trial that a recombinant subunit vaccine based on the gamma variant of SARS-CoV-2 exhibits a satisfactory safety profile, and induces a broad booster response of neutralizing antibodies and a booster effect on T cell immunity in individuals previously immunized with different SARS-CoV-2 vaccine platforms.
- Karina A. Pasquevich
- , Lorena M. Coria
- & Juliana Cassataro
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Article
| Open AccessSignatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins
The burden of chronic hepatitis C virus infection is exacerbated by the lack of an effective vaccine. In this work, authors use a recombinant permuted (E2E1) HCV glycoprotein design to analyze the binding of different VH1-69-derived AR3-directed broadly neutralizing antibodies to the viral envelope glycoprotein.
- Joan Capella-Pujol
- , Marlon de Gast
- & Kwinten Sliepen
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Article
| Open AccessStructure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies
HCV vaccine development has been challenged by difficulties in the biochemical preparation of E1E2 ectodomains. Here, the authors structurally characterize an engineered soluble E1E2 ectodomain complexed with broadly neutralizing antibodies, revealing it adopts a native fold amenable for vaccine design.
- Matthew C. Metcalf
- , Benjamin M. Janus
- & Gilad Ofek
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Article
| Open AccessA ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates
Here the authors develop a ferritin-based protein nanoparticle vaccine candidate for SARS-CoV-2, and show induction of neutralizing antibodies to variants of concern, including Omicron BQ.1, in non-human primates after initial immunization and a booster dose.
- Payton A.-B. Weidenbacher
- , Mrinmoy Sanyal
- & Peter S. Kim
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Article
| Open AccessSingle-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates
Here the authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.
- Yi-Nan Zhang
- , Jennifer Paynter
- & Jiang Zhu
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Article
| Open AccessBeta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates
Waning protective efficacy of mRNA-based booster vaccinations has been observed against newly emerging SARS-CoV-2 variants of concern. In this work, Pavot et al. formulate a monovalent Beta vaccine and demonstrate durable cross-neutralising antibody responses in non-human primates, against a spectrum of variants.
- Vincent Pavot
- , Catherine Berry
- & Valerie Lecouturier
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Article
| Open AccessSafety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults
Here the authors present results from a randomized, double-blinded Phase 1 clinical trial, testing a thermostable presentation of a clinical-stage adjuvanted subunit tuberculosis vaccine candidate. The vaccine candidate is safe and well tolerated, and elicits comparable or improved immune responses compared to the non-thermostable presentation.
- Zachary K. Sagawa
- , Cristina Goman
- & Christopher B. Fox
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Article
| Open AccessThe cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
A gB/MF59 vaccine candidate for human cytomegalovirus (HCMV) provided partial protection in organ transplant patients. Here, the authors identify antibody responses in trial participants that target virally infected cells to control cell-to-cell spread of HCMV, providing a potential mechanism for the observed protection.
- A. C. Gomes
- , I. A. Baraniak
- & M. B. Reeves
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Article
| Open AccessInduction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate
E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.
- Kwinten Sliepen
- , Laura Radić
- & Rogier W. Sanders
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Article
| Open AccessMucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
Current vaccines against SARS-CoV-2 reduce mortality but are less effective in preventing infection. Here the authors show that intranasal vaccination with a subunit vaccine including an TLR2-stimulating adjuvant induces strong neutralising antibody and T-cell responses against SARS-CoV-2 in the lungs that protect against infection.
- Anneliese S. Ashhurst
- , Matt D. Johansen
- & Warwick J. Britton
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Article
| Open AccessDurability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19
Here, the authors report results from a Phase 1 trial with an AS03-adjuvanted, plant-based virus-like particle displaying the spike protein of the ancestral SARS-CoV-2. Six months post-second dose, they observe good neutralizing antibody titers and T cell responses to ancestral virus and variants of concern in participants.
- Philipe Gobeil
- , Stéphane Pillet
- & Brian J. Ward
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| Open AccessDynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack
The membrane-proximal external region of HIV-1 spike protein is a broadly neutralizing antibody target. Here, cryo-electron microscopy and molecular dynamics reveal spontaneous ectodomain tilting, a vulnerability exploitable for vaccine design.
- Shuang Yang
- , Giorgos Hiotis
- & Thomas Walz
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Article
| Open AccessNeutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion
The Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1) is a prime vaccine candidate for malaria. Here, the authors structurally and functionally characterise a panel of naturally acquired MSP-1 specific antibodies to identify one with potent broadly neutralising activity and better understand immune evasion mechanisms.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
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Article
| Open AccessA self-assembled trimeric protein vaccine induces protective immunity against Omicron variant
The SARS-CoV-2 Omicron variant has quickly become the predominant circulating variant, due to the high transmissibility and immune escape. Here, the authors develop a trimeric protein vaccine candidate and show a sustained humoral immune response, and protection from challenge (Omicron and Delta) in various animal models.
- Cai He
- , Jingyun Yang
- & Xiawei Wei
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Article
| Open AccessA randomized controlled trial of heterologous ChAdOx1 nCoV-19 and recombinant subunit vaccine MVC-COV1901 against COVID-19
Public safety concern of the ChAdOx1 vaccine has led to an alternative immunisation strategy against SARS-CoV-2, with this heterologous schedule widely adopted and officially recommended in many countries. Here, the authors report the immunogenicity and safety outcomes of heterologous prime-boost immunisation with ChAdOx1 and a spike-2P subunit vaccine in a single-blinded, randomised trial.
- Chih-Jung Chen
- , Lan-Yan Yang
- & Kuan-Ying A. Huang
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Article
| Open AccessQuadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants
Emerging SARS-CoV-2 variants with multiple mutations raise concerns on vaccine effectiveness. Here, Kang et al. report that a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and three different VOCs confer protection against SARS-CoV-2 variants in mice.
- Yin-Feng Kang
- , Cong Sun
- & Mu-Sheng Zeng
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Article
| Open AccessProtein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization against SARS-CoV-2 variants of concern in non-human primates
Emerging SARS-CoV-2 variants of concern (VOCs) raise questions on vaccine effectiveness. Here, the authors show that an adjuvanted protein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization of VOC, including omicron, in non-human primates.
- Vincent Pavot
- , Catherine Berry
- & Valerie Lecouturier
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Article
| Open AccessStructure-based design of prefusion-stabilized human metapneumovirus fusion proteins
The degree to which the conformation of the human metapneumovirus fusion (F) protein affects immunogenicity has been debated. Here, Hsieh et al. engineer prefusion-stabilized F variants with enhanced thermostability that elicit higher neutralizing antibody titers in mice than postfusion F.
- Ching-Lin Hsieh
- , Scott A. Rush
- & Jason S. McLellan
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Article
| Open AccessDifferential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines
Here the authors show that an HIV vaccine in non-human primates that focuses antibodies on the V1V2 region of gp120 is superior to infection or immunization with whole envelope vaccines for inducing V1V2 antibodies with anti-viral functions that correlate with protection.
- Svenja Weiss
- , Vincenza Itri
- & Susan Zolla-Pazner
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Article
| Open AccessA Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients
Modulating the host immune response during tuberculosis is an emerging and critical advance in the therapeutic approach. Here the authors present data from a first-in-human phase I/II randomised trial on the safety and immunogenicity of adjuvant therapy of the H56:IC31 vaccine and cyclooxygenase-2 inhibitors in patients with tuberculosis.
- Synne Jenum
- , Kristian Tonby
- & Anne Ma Dyrhol-Riise
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Article
| Open AccessPre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination
Understanding individual variations in the response to seasonal influenza vaccines has broad implications from basic immunology to public health. Here authors show that influenza hemagglutinin-specific T and B cell responses are determined by the pre-vaccination immune phenotype and vaccination history of recipients.
- Katharina Wild
- , Maike Smits
- & Tobias Boettler
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Article
| Open AccessA Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin
Tuberculosis (TB) subunit vaccines have been investigated as boosters for BCG-induced immunity. Here, the authors design a TB subunit vaccine that doesn't share antigens with BCG and show that co-administration of the two vaccines broadens the T cell response to TB and increases protection.
- Joshua S. Woodworth
- , Helena Strand Clemmensen
- & Rasmus Mortensen
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Article
| Open AccessAfucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
Here, Larsen et al. describe differences in Fc fucosylation of P. falciparum PfEMP1-specific IgG produced in response to natural infection versus VAR2CSA-type subunit vaccination, which leads to differences in the ability to induce FcγRIIIa-dependent natural killer cell degranulation.
- Mads Delbo Larsen
- , Mary Lopez-Perez
- & Gestur Vidarsson
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Article
| Open AccessTargeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques
In this study, Marlin et al. provide insights into the potential use of subunit vaccines that induce a high level of protection against SARS-CoV-2 in animal models.
- Romain Marlin
- , Veronique Godot
- & Roger Le Grand
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Article
| Open AccessPolyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Here, the authors present cryoEMPEM, a method for high-resolution structural analysis of vaccine-elicited polyclonal antibody responses. They apply cryoEMPEM in combination with standard serology experiments to characterize the polyclonal antibody (pAb) responses elicited in rhesus macaques by HIV Env trimer immunogens and were able to determine up to 8 different polyclonal antibody structures in complex with their respective antigen from a single cryoEM dataset.
- Aleksandar Antanasijevic
- , Leigh M. Sewall
- & Andrew B. Ward
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Article
| Open AccessSARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung
Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection.
- Nanda Kishore Routhu
- , Narayanaiah Cheedarla
- & Rama Rao Amara
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Article
| Open AccessSingle-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.
- Linling He
- , Anshul Chaudhary
- & Jiang Zhu
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Article
| Open AccessA human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes
Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.
- Camila H. Coelho
- , Wai Kwan Tang
- & Patrick E. Duffy
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Article
| 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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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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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