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| Open AccessDevelopment of a skin- and neuro-attenuated live vaccine for varicella
Current varicella vaccines retain neurovirulence and can establish latency and reactivate. Here, the authors present preclinical results of a rationally-designed, skin- and neuro-attenuated varicella vaccine candidate, v7D, showing its attenuation in human skin and neuronal cells and its immunogenicity in small animal models and nonhuman primates
- Wei Wang
- , Dequan Pan
- & Ningshao Xia
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Article
| Open AccessInduction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer
HIV envelope is a target for vaccine development, but induction of broadly neutralizing antibodies has been difficult. Here, the authors show that electroporation with a synthetic DNA vaccine construct allows in vivo production of HIV envelope native like trimers to induce autologous tier-2 neutralizing antibodies targeting a C3/V5 epitope in mice.
- Ziyang Xu
- , Susanne Walker
- & Daniel W. Kulp
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| Open AccessCost-effectiveness of routine adolescent vaccination with an M72/AS01E-like tuberculosis vaccine in South Africa and India
The M72/AS01E tuberculosis vaccine has shown 50% efficacy in preventing pulmonary TB disease in infected 18–50 year olds. Here, the authors demonstrate that, in most scenarios modelled, vaccination of adolescents would also be cost effective in two high incidence settings, South Africa and India.
- Rebecca C. Harris
- , Matthew Quaife
- & Richard G. White
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| Open AccessImpacts of rapid mass vaccination against SARS-CoV2 in an early variant of concern hotspot
Schwaz, Austria, experienced SARS-CoV-2 outbreaks caused by variants of concern in early 2021 and conducted a mass vaccination campaign in response, with 70% of the adult population vaccinated after 5 days. Here, the authors show that this campaign resulted in reduced infections and hospitalisations.
- Jörg Paetzold
- , Janine Kimpel
- & Hannes Winner
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| Open AccessA molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice
Adjuvants provide additional impetus for the immune response to vaccination regimens, however their modes of activity and impact on particular compartments of the immune response are currently not well understood. Here the authors perform high resolution assessment of the immune response to a well-established vaccination model and show innate immune transcriptomic and epigenomic alterations of innate cells in the lymph nodes following vaccination.
- Audrey Lee
- , Madeleine K. D. Scott
- & Bali Pulendran
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| Open AccessMultimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong
Adverse events resulting from COVID-19 vaccination are a public health concern and it is not known whether pre-existing conditions may impose an increased risk. Here, using electronic health records from Hong Kong, the authors show that adverse events are rare for all groups, and there is no evidence of risk modification due to multimorbidity.
- Francisco Tsz Tsun Lai
- , Lei Huang
- & Ian Chi Kei Wong
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Article
| Open AccessSingle dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus
Here the authors generate a live-attenuated Zika vaccine based on a clinically proven dengue virus serotype-2 vaccine backbone and show that one dose protects mice and non-human primates from Zika virus infection.
- Whitney R. Baldwin
- , Holli A. Giebler
- & Claire Y.-H. Huang
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| Open AccessImpact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants
Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.
- Edward P. K. Parker
- , Christina Bronowski
- & Miren Iturriza-Gómara
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| Open AccessA randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults
Here the authors provide the interim analysis of an ongoing phase 1/2 study of the BNT162b2 vaccine in healthy Japanese adults. They report mainly mild to moderate local reactions and no serious adverse events as well as good antibody induction one month after the second dose.
- Miwa Haranaka
- , James Baber
- & Stephen Lockhart
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| Open AccessSerological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England
The UK extended the interval until the second COVID-19 vaccine dose up to 12 weeks. Here, the authors show in a cohort of 750 participants aged 50–89 years that the extended schedule results in higher antibody titers and estimate a higher vaccine effectiveness for the extended schedule.
- Gayatri Amirthalingam
- , Jamie Lopez Bernal
- & Mary E. Ramsay
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Article
| Open AccessProtective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
While current COVID-19 vaccines provide certain protection, more effective vaccination strategies are still desirable. Here the authors show, using mouse vaccination models, that priming with a systemic mRNA and boosting with an intranasal adenoviral vector vaccine induces comprehensive T cell and mucosal immunity.
- Dennis Lapuente
- , Jana Fuchs
- & Matthias Tenbusch
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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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| 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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| 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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| Open AccessCorrelation of SARS-CoV-2-breakthrough infections to time-from-vaccine
The duration of effectiveness of SARS-CoV-2 vaccination is not yet known. Here, the authors present preliminary evidence of BNT162b2 vaccine waning across all age groups above 16, with a higher incidence of infection in people who received their second dose early in 2021 compared to later in the year.
- Barak Mizrahi
- , Roni Lotan
- & Tal Patalon
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| Open AccessPotential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine
The ChAdOx1 nCoV-19 vaccine requires two doses, but under limited supply single dose regimens have also been considered. Here, the authors show using static transmission modelling that under certain conditions it is optimal to more expediently administer a single dose to a larger proportion of the population.
- Ricardo Aguas
- , Anouska Bharath
- & Rima Shretta
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| Open AccessA live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters
Here the authors generate a measles virus-based vaccine expressing SARSCoV-2 spike protein and show immunogenicity and protection in mice and hamsters, including neutralization of circulating variants of concerns in vitro.
- Phanramphoei N. Frantz
- , Aleksandr Barinov
- & Frédéric Tangy
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| Open AccessBNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women
Maternal antibodies can reduce risk of infection of infants. Here, the authors show induction of IgG and IgA antibodies in breastmilk and serum of ten lactating women after immunization with the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine.
- Michal Rosenberg-Friedman
- , Aya Kigel
- & Yariv Wine
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| Open AccessA Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses
Here the authors show that a Newcastle disease virus based COVID-19 vaccine expressing a stabilized spike protein induces protective immunity in small animal models and reduces replication of variants of concerns. This vaccine candidate can be produced by influenza virus vaccine manufactures around the world.
- Weina Sun
- , Yonghong Liu
- & Peter Palese
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| Open AccessSARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers
Several COVID-19 vaccines have shown good efficacy in clinical trials. Here, the authors provide real world effectiveness data in a group of BNT162b2 vaccinated health care workers and find that breakthrough infections are asymptomatic or mild.
- Francesca Rovida
- , Irene Cassaniti
- & Fausto Baldanti
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| Open AccessChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7
Emerging SARS-CoV-2 variants raise concerns about vaccine effectiveness. Here, the authors show that the ChAdOx1 nCoV-19 (AZD1222) vaccine protects Syrian hamsters from pulmonary infection and disease after infection with SARS-CoV-2 B.1.351 or B.1.1.7 variants.
- Robert J. Fischer
- , Neeltje van Doremalen
- & Vincent J. Munster
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| Open AccessSARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques
Several COVID-19 vaccines have received emergency approval, but durability of protection is unclear. Here, the authors describe correlates of protection (CoP) for the Ad26.COV2.S vaccine in rhesus macaques and report that CoP predict the protection observed 6 months post vaccination.
- Ramon Roozendaal
- , Laura Solforosi
- & Roland Zahn
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| Open AccessEfficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil
Emerging variants of SARS-CoV-2 raise concerns about vaccine efficiency. Here, the authors present a post-hoc analysis for the ChAdOx1 nCoV-19 (AZD1222) vaccine trial in Brazil and provide efficacy against symptomatic COVID-19 caused by the Zeta (P.2) and other variants.
- Sue Ann Costa Clemens
- , Pedro M. Folegatti
- & Rafael Zimmer
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| 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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| Open AccessSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation
The Spike protein of SARS-CoV-2 has a C-terminal cytoplasmic tail. Here the authors show that this tail binds trafficking machinery via sequences that appear optimised to ensure that Spike accumulates at the site of viral budding in the Golgi but that some can also traffic to the cell surface to induce syncytia formation.
- Jérôme Cattin-Ortolá
- , Lawrence G. Welch
- & Sean Munro
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| 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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| Open AccessA modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity
Successful cancer immune therapy correlates with a T cell-inflamed tumour microenvironment. Authors show here that co-administration of a self-adjuvanting protein vaccine and an antigen-expressing oncolytic virus in an optimised regimen strongly enhances T cell immunogenicity and may turn non-inflamed tumours proinflammatory and less resistant to checkpoint blockade therapy.
- Krishna Das
- , Elodie Belnoue
- & Guido Wollmann
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| Open AccessNeutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum
Here, the authors show that neutralization of human sera from both BNT162b2 vaccine recipients and from convalescent COVID-19 patients is less efficient against SARS- CoV-2 variants B.1.1.7 and B.1.351 and negatively associated with patient age.
- Timothy A. Bates
- , Hans C. Leier
- & Fikadu G. Tafesse
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Article
| Open AccessTwo doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern
Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.
- Donal T. Skelly
- , Adam C. Harding
- & William S. James
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| Open AccessAn amphiphilic dendrimer as a light-activable immunological adjuvant for in situ cancer vaccination
Immunological adjuvants are a crucial component of cancer vaccines. Here the authors design a light-activable immunological adjuvant, based on hypoxia-responsive amphiphilic dendrimer nanoparticles loaded with a photodynamic agent, promoting anti-tumor immune responses in preclinical cancer models.
- Yongchao Wang
- , Ningqiang Gong
- & Xing-Jie Liang
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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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| Open AccessViral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment
Lymphocytic choriomeningitis virus (LCMV)-based viral vectors have been shown to induce potent antitumor immune responses. Here the authors show that a LCMV-based vaccine vector remodels the tumor-associated fibroblastic stroma, sustaining CD8+ T cell activation and reducing tumor growth in a preclinical model of melanoma.
- Sandra S. Ring
- , Jovana Cupovic
- & Lukas Flatz
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| Open AccessMalignant cerebral infarction after ChAdOx1 nCov-19 vaccination: a catastrophic variant of vaccine-induced immune thrombotic thrombocytopenia
Vaccination is an effective strategy in suppressing COVID-19 pandemic, but rare adverse effects have been reported, including cerebral venous thrombosis. Here the authors report two cases of middle cerebral artery infarct within 9-10 days following ChAdOx1 nCov-19 vaccination that also manifest pulmonary and portal vein thrombosis.
- M. De Michele
- , M. Iacobucci
- & D. Toni
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| Open AccessA single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.
- Pedro M. Folegatti
- , Kate Harrison
- & Arturo Reyes-Sandoval
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| Open AccessImmune responses to a single dose of the AZD1222/Covishield vaccine in health care workers
Here the authors show in a large cohort of healthcare workers that one dose of the AZD1222 vaccine seroconverts 92.9% of vaccinees, irrespective of age and gender, and results in high antibody titers to wild-type SARS-CoV-2 but only low titers to the B.1.351 variant.
- Chandima Jeewandara
- , Achala Kamaladasa
- & Gathsaurie Neelika Malavige
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Article
| Open AccessNeutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants
Here, the authors characterize the neutralization capacity of post-Sputnik V vaccination sera against SARS-CoV-2 variants of concern B.1.1.7 (alpha) and B.1.351 (beta), showing the latter to exhibit resistance to neutralization in vitro.
- Satoshi Ikegame
- , Mohammed N. A. Siddiquey
- & Benhur Lee
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Article
| Open AccessCVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2
Emerging SARS-CoV-2 variants with mutations in the spike protein raise concerns regarding vaccine efficacy. Here, the authors show that two spike encoding mRNA vaccines in preclinical and clinical development protect human ACE2 mice from the B.1.351 variant of concern and ancestral B BavPat1.
- Donata Hoffmann
- , Björn Corleis
- & Martin Beer
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Article
| Open AccessCOVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants
Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al. show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.
- Pinja Jalkanen
- , Pekka Kolehmainen
- & Ilkka Julkunen
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Article
| Open AccessBNT162b2 vaccine uptake and effectiveness in UK healthcare workers – a single centre cohort study
Several vaccines for COVID-19 have received emergency approval. Here, the authors describe BNT162B2 vaccine uptake and effectiveness among UK healthcare workers in a single centre cohort study during a time of high community COVID-19 prevalence.
- Tariq Azamgarhi
- , Michelle Hodgkinson
- & Simon Warren
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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 AccessOptimizing vaccine allocation for COVID-19 vaccines shows the potential role of single-dose vaccination
Most COVID-19 vaccines require two doses but a single dose provides partial protection, so it is unclear how best to prioritize vaccine distribution in the context of limited supply. Here, the authors show that campaigns in which some age groups receive one dose while others receive both doses may be optimal.
- Laura Matrajt
- , Julia Eaton
- & Holly Janes
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Article
| Open AccessImmune response to SARS-CoV-2 variants of concern in vaccinated individuals
Here, the authors characterize the antibody response from vaccinated (Pfizer BNT-162b2), infected and uninfected individuals against emerging variants of concern of SARS-CoV-2, finding reduced neutralization of a South African isolate. High IgG titers in the saliva of vaccinees suggest that transmission may be reduced.
- Matthias Becker
- , Alex Dulovic
- & Nicole Schneiderhan-Marra
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Article
| Open AccessThe metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses
T follicular helper (TFH) cell numbers are increased after vaccination and fewer of these cells might result in reduced vaccine responses. Here the authors show in mice and humans that leptin promotes TFH differentiation and that low leptin levels can impair TFH response to vaccines and virus protection in mice.
- Jun Deng
- , Qian Chen
- & Di Yu
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Article
| Open AccessHeterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice
Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.
- Alexandra J. Spencer
- , Paul F. McKay
- & Teresa Lambe
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Article
| Open AccessCirculation of pertussis and poor protection against diphtheria among middle-aged adults in 18 European countries
Recent outbreaks of pertussis have highlighted the importance of surveillance of vaccine-preventable diseases. Here, the authors performed a cross-sectional seroprevalence study of pertussis, diphtheria, and tetanus in Europe and found evidence of circulation of pertussis in middle-aged adults.
- Guy Berbers
- , Pieter van Gageldonk
- & Jussi Mertsola
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| Open AccessCharacterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein
The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.
- Pui Wang
- , Siu-Ying Lau
- & Honglin Chen
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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 AccessDual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice
Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.
- Eva Conde
- , Romain Bertrand
- & Laurent L. Reber
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Article
| Open AccessEpididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling
Zika virus can be sexually transmitted. Here, Pletnev et al. show in an immunocompromised mouse model that the epithelial cells of the epididymis, rather than cells of the testis, vas deferens, prostate, or seminal vesicles, are the most likely source of male-to-female sexually transmitted ZIKV genomes.
- Alexander G. Pletnev
- , Olga A. Maximova
- & Konstantin A. Tsetsarkin