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Malaria 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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Article
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Prior 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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An 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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BCG 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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Distinct 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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Quantitative 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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Early 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
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FHL1 promotes chikungunya and o’nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design
FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o’nyong-nyong infections but not Ross River or mayaro virus infection.
- Wern Hann Ng
- , Xiang Liu
- & Suresh Mahalingam
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An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models
Here, the authors report the generation of a live but defective SARS-CoV-2 virus that is envelope-deficient and expresses human interferon beta. They show that nasal vaccination enhances mucosal and lung T cell response and provides pan-sarbecovirus protection in small animals.
- Chun-Kit Yuen
- , Wan-Man Wong
- & Kin-Hang Kok
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Infection- or AZD1222 vaccine-mediated immunity reduces SARS-CoV-2 transmission but increases Omicron competitiveness in hamsters
The impact of various immune statuses on SARS-CoV-2 transmission is unclear. Here, the authors used transmission chain experiments in hamsters to show better transmission prevention after intranasal vaccination and previous infection. Higher humoral responses against Delta may provide a competitive advantage to Omicron.
- Julia R. Port
- , Claude Kwe Yinda
- & Vincent J. Munster
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Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals
In this work, Otter et al. compared the humoral immune responses induced by MPXV infection and Smallpox vaccination. Although comparable responses were observed, infection- or vaccination specific serological markers were identified enabling discrimination between vaccinated and infected individuals.
- Ashley D. Otter
- , Scott Jones
- & Bassam Hallis
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Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques
The route of vaccine administration is known to effect the induction of immune response and the quality of such immunity. Here the authors show that intradermal but not intramuscular vaccination using live-attenuated vaccinia-based SHIV vaccine confers protection in the SHIV model in female macaques and characterise the induced immune response.
- Venkata S. Bollimpelli
- , Pradeep B. J Reddy
- & Rama R. Amara
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Intranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters
Understanding the utility of SARS -CoV-2 vaccination platforms and strategies through the emerging pandemic and beyond are critical to understanding the efficacy of such interventions. Here the authors assess nasal delivery of an influenza virus based viral vector for vaccination against SARS-CoV-2 in a hamsters model and assess the induced immunity.
- Liang Zhang
- , Yao Jiang
- & Ningshao Xia
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Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants
Mucosal immune response is important to determine protective efficiency of intranasal vaccines. Here, the authors analyse mucosal immunogenicity, transmissibility, efficacy, and boosting effects of an attenuated SARS-CoV-2 vaccine platform in Syrian hamsters and mice.
- Charles B. Stauft
- , Prabhuanand Selvaraj
- & Tony T. Wang
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An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters
Current vaccines are less efficient in preventing infection. Here, the authors show that an intranasal vaccine (DelNS1-RBD) based on a live attenuated influenza virus induces robust levels of neutralizing antibodies and T cells and prevents replication of SARS-CoV-2 Delta and Omicron variants in respiratory tissues.
- Shaofeng Deng
- , Ying Liu
- & Honglin Chen
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A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity
Here, the authors report a live chimeric DENV2/4 EDII virus, encoding DENV2 and DENV4 neutralizing epitopes, that replicates efficiently in primates and simultaneously elicits neutralizing DENV2 and DENV4 type-specific antibodies, providing domain-specific diagnostic reagents and simplified vaccine strategies.
- Ellen Young
- , Boyd Yount
- & Ralph S. Baric
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Rapid protection induced by a single-shot Lassa vaccine in male cynomolgus monkeys
Lassa virus vaccination is impeded by the limited capacity of vaccine candidates to induce rapid protection. In this study, the authors found that a single shot of a measles-based Lassa vaccine protected nonhuman primates 16 or 8 days after vaccination.
- Mathieu Mateo
- , Stéphanie Reynard
- & Sylvain Baize
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Direct intranodal tonsil vaccination with modified vaccinia Ankara vaccine protects macaques from highly pathogenic SIVmac251
Mucosal surfaces are a primary route of HIV entry, yet the compartmentalisation between mucosal and peripheral immune systems remain a challenge for HIV vaccine candidates. Authors utilise a combination of intranodal tonsil MALT and systemic vaccination in the rhesus macaque model to explore immune responses and protection from highly pathogenic simian homologue of HIV.
- Jeffy G. Mattathil
- , Asisa Volz
- & Joseph J. Mattapallil
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Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase
In this work, authors provide a proof-of-concept study showing that deubiquitinating enzyme inactivation in MERS-CoV leads to attenuation in mice, and protection against a lethal challenge.
- Sebenzile K. Myeni
- , Peter J. Bredenbeek
- & Marjolein Kikkert
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Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters
Examples of effective live attenuated viral vaccines include the measles, mumps and rubella vaccine, as well as the chickenpox vaccine. In this work, the authors engineer a live attenuated SARS-CoV-2 virus that demonstrates attenuation in numerous in vivo models, and protection in hamsters upon challenge.
- Shufeng Liu
- , Charles B. Stauft
- & Tony T. Wang
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Updated vaccine protects against SARS-CoV-2 variants including Omicron (B.1.1.529) and prevents transmission in hamsters
Currently licensed COVID-19 vaccines are based on antigen sequences of early SARS-CoV-2 isolates, despite the prevalence of variants of concerns escaping vaccine-mediated protection. Using their updated yellow fever 17D vectored candidate, here, authors assess neutralising antibody responses against variants of concern, and demonstrate protection and reduced transmission in a hamster model.
- Sapna Sharma
- , Thomas Vercruysse
- & Kai Dallmeier
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A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions
A live-attenuated COVID vaccine could enrich the current vaccine portfolio. Here, Liu et al. engineer a live-attenuated SARS-CoV-2 vaccine candidate by deleting four viral accessory genes and show immunogenicity and protection in mice and hamsters.
- Yang Liu
- , Xianwen Zhang
- & Pei-Yong Shi
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Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa
Here the authors show that controlled human malaria infection with a Brazilian parasite highly divergent from vaccine and West African field strains can provide estimates of vaccine efficacy in Mali, and could replace field testing, streamlining vaccine development.
- Joana C. Silva
- , Ankit Dwivedi
- & Stephen L. Hoffman
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Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer
Vaccination with BCG has been shown to induce a pre-priming effect in innate immune cells termed trained immunity. Here the authors re-engineer the BCG vaccine and show augmented immune responses, enhanced induction of trained immunity and improved antitumor efficacy in pre-clinical models of bladder cancer.
- Alok Kumar Singh
- , Monali Praharaj
- & Trinity J. Bivalacqua
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Development 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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Single 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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Impact 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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A 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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A 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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Article
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ChAdOx1 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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Viral 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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Neutralizing 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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Characterization 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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Epididymal 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
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Characterization 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
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Development 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
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An 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
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Prior 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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Article
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A 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
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Maternal 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
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Viral 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
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Innate 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
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Dissecting 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
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Routes of Zika virus dissemination in the testis and epididymis of immunodeficient mice
The mechanisms of ZIKV persistence in the male reproductive tract (MRT) are poorly understood. Here, Tsetsarkin et al. applied microRNA-targeting approach to trace routes of ZIKV dissemination in the testis and epididymis and to generate immunogenic live-attenuated ZIKV vaccine candidate, restricted for MRT infection.
- Konstantin A. Tsetsarkin
- , Olga A. Maximova
- & Alexander G. Pletnev
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Article
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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses
Humanized mice are an enabling technology to explore human immunity and disease. Here, Douam et al. provide an in-depth comparison of immune responses to yellow fever vaccine in human vaccinees, conventional and second-generation humanized mice and define a workflow to evaluate and refine these models.
- Florian Douam
- , Carly G. K. Ziegler
- & Alexander Ploss
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Human milk oligosaccharides, milk microbiome and infant gut microbiome modulate neonatal rotavirus infection
Neonatal rotavirus infections are associated with gastrointestinal symptoms in some settings, but the role of host factors in clinical presentation is unclear. Here, Ramani et al. show that human milk oligosaccharides and microbiome are associated with symptomatic infection with neonatal strain G10P[11].
- Sasirekha Ramani
- , Christopher J. Stewart
- & Mary K. Estes
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Article
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Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning
Clinical trials for the CYD-TDV dengue vaccine showed that vaccine efficacy varies with prior dengue exposure, but baseline serostatus is only known for 12% of subjects. Here, Dorigatti et al. use machine learning to impute baseline serostatus and determine vaccine efficacy by baseline serostatus, age and dengue serotype.
- I. Dorigatti
- , C. A. Donnelly
- & N. M. Ferguson
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A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein
Current Zika virus (ZIKV) subunit vaccine development largely focuses on prM and E proteins, and the role of NS1 for immune response and protection is unclear. Here, Li et al. develop an attenuated VSV-based vaccine expressing a ZIKV prM-E-NS1 polyprotein and characterize immune response and protection in mice.
- Anzhong Li
- , Jingyou Yu
- & Jianrong Li
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Article
| Open Access
A systematic approach to the development of a safe live attenuated Zika vaccine
A Zika virus (ZIKV) vaccine should provide long-lasting immunity, which may be achieved with a live-attenuated vaccine. Here, Kwek et al. select an interferon-restricted, attenuated ZIKV variant and evaluate replication and immunogenicity in mouse and mosquito models.
- Swee Sen Kwek
- , Satoru Watanabe
- & Eng Eong Ooi
A live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections