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| Open AccessA combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates
Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.
- Ivy Phung
- , Kristen A. Rodrigues
- & Shane Crotty
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Article
| Open AccessIL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
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Article
| Open AccessStructural basis for the toxicity of Legionella pneumophila effector SidH
Legionella pneumophila secretes hundreds of effectors to facilitate infection. Here, Sharma et al show that the virulence effector SidH adopts a unique α-helical conformation, leading to toxicity via tRNA binding site and resolve the structural basis of SidH regulation through ubiquitination.
- Rahul Sharma
- , Michael Adams
- & Sagar Bhogaraju
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Article
| Open AccessDistinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time
Evidence from trials suggests SARS-CoV-2 binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether this is accurate in the context of variants of concerns, or in the event of prior infection or vaccination remains unclear. Authors explore the performance of receptor binding domain IgG thresholds in predicting a level of neutralising capacity that has demonstrated protection against infection in vaccine trials
- Grace Kenny
- , Sophie O’Reilly
- & Patrick Mallon
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Article
| Open AccessProduction of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
As leishmaniasis control programs and new vaccines are advancing, it is necessary to re-introduce the leishmanin skin test to monitor transmission and immunity. This study describes the generation and validation of a new leishmanin skin test antigen for future re-introduction into endemic countries.
- Ranadhir Dey
- , Jalal Alshaweesh
- & Greg Matlashewski
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Article
| Open AccessDefining neutralization and allostery by antibodies against COVID-19 variants
Here, Tulsian et al. identified the effect of biologically relevant full-length IgG binding on the Spike protein from different SARS-CoV-2 variants to comprehensively understand the mechanisms of antibody evasion, towards the development of better antiviral strategies.
- Nikhil Kumar Tulsian
- , Raghuvamsi Venkata Palur
- & Paul Anthony MacAry
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Comment
| Open AccessLessons for cross-species viral transmission surveillance from highly pathogenic avian influenza Korean cat shelter outbreaks
In this Comment, the authors describe recent outbreaks of highly pathogenic avian influenza in cat shelters in Seoul, South Korea. They discuss potential routes of transmission and describe implications for surveillance of spillover infections in animals in non-agricultural settings.
- Younjung Kim
- , Guillaume Fournié
- & Pierre Nouvellet
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Article
| Open AccessSelf-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration
Infected bone defects are a major challenge in orthopedic treatment. Here, the authors develop an electroactive mineralized scaffold that achieves nearly complete in situ healing of infected bone in rats, rabbits and beagle dogs.
- Zixin Li
- , Danqing He
- & Yan Liu
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Article
| Open AccessInferring bacterial transmission dynamics using deep sequencing genomic surveillance data
Studying rare genetic changes that arose as an infectious bacterium spread between lab mice, here the authors show that using the relative abundance of any changes rather than just whether they occurred can more precisely identify who likely infected who.
- Madikay Senghore
- , Hannah Read
- & Siouxsie Wiles
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Article
| Open AccessAntiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection
Bats are natural reservoirs for several zoonotic viruses including SARS-CoV-2 thus there is a need to better define bat antiviral responses. Here, Hashimi et al. profile antiviral responses to SARS-CoV-2 in bat intestinal organoids finding that interferon and regenerative responses where induced.
- Marziah Hashimi
- , T. Andrew Sebrell
- & Diane Bimczok
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Article
| Open AccessImpact of COVID-19 on mortality in coastal Kenya: a longitudinal open cohort study
SARS-CoV-2-associated mortality estimates for sub-Saharan Africa are uncertain due to lack of comprehensive surveillance systems. Here, the authors analyse data from a detailed surveillance system in Kilifi, Kenya and find that excess mortality rates were relatively low, except for older adults.
- M. Otiende
- , A. Nyaguara
- & J. A. G. Scott
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Article
| Open AccessEffectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile
This study assesses the effectiveness of a second COVID-19 mRNA booster vaccine against severe disease using data from Chile. The authors find that the effectiveness of the second mRNA booster was high with a range of different background vaccination schemes, but there was evidence of waning over time.
- Alejandro Jara
- , Cristobal Cuadrado
- & Rafael Araos
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Article
| Open AccessPasteurella sp. associated with fatal septicaemia in six African elephants
A series of unexplained elephant mortalities occurred in northwest Zimbabwe in 2020. Here the authors show that six elephants died of bacterial septicaemia associated with a little-reported Pasteurella species.
- Chris M. Foggin
- , Laura E. Rosen
- & Falko Steinbach
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Article
| Open AccessLong-term health impacts of COVID-19 among 242,712 adults in England
The duration of symptomatic COVID-19 and its impacts on health and quality of life are not well understood. In this study, the authors report results from a survey of ~275,000 adults in England and find that persistent COVID-19 is relatively rare but is associated with poorer mental health and health-related quality of life.
- Christina J. Atchison
- , Bethan Davies
- & Paul Elliott
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Article
| Open AccessC-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity
Receptor dimerization can modulate immune responses during various microbial infections. Here, the authors show that C-type lectin receptor-2d (CLEC2D) negatively regulates antifungal immunity through forming homodimers or heterodimers with TLR2.
- Fan Li
- , Hui Wang
- & Xin-Ming Jia
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Article
| Open AccessPathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections
Group A streptococcus causes a wide range of human diseases and significantly contributes to morbidity and mortality worldwide. Here, Toledo et al show how streptococcus alters the structure and function of endogenous and therapeutic antibodies during infection and how this is affected by the host microenvironment.
- Alejandro Gomez Toledo
- , Eleni Bratanis
- & Johan Malmström
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Article
| Open AccessIndividual level analysis of digital proximity tracing for COVID-19 in Belgium highlights major bottlenecks
Digital proximity tracing apps were widely used during the COVID-19 pandemic but have not been thoroughly evaluated. Here, the authors use data from students in Leuven, Belgium and estimate that apps notified only ~4% exposed contacts, had a 1–2 day delay for notification, and identified fewer infected contacts than manual contact tracing.
- Caspar Geenen
- , Joren Raymenants
- & Emmanuel André
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Article
| Open AccessActivation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination
Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.
- Malika Aid
- , Kathryn E. Stephenson
- & Dan H. Barouch
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Article
| Open AccessStructure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir
The HIV-1 entry inhibitor temsavir prevents the interaction of the envelope glycoprotein with its cellular receptor. Here, authors apply CryoEM to show that HIV-1 clade AE resistance to temsavir is a combination of the residue at position 375 (His) and mutations in the gp120 mobile layers. Mutation of His375 to Ser/Thr and reversion of the layer mutations are required to restore temsavir sensitivity.
- Jérémie Prévost
- , Yaozong Chen
- & Marzena Pazgier
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Article
| Open AccessA genomic appraisal of invasive Salmonella Typhimurium and associated antibiotic resistance in sub-Saharan Africa
Invasive Salmonella Typhimurium bloodstream infection causes a significant public health burden in sub-Saharan Africa. Here, the authors analyse whole genome sequences of 1,302 S. Typhimurium isolates from Africa and describe its evolution, geographic spread, and antimicrobial resistance characteristics.
- Sandra Van Puyvelde
- , Tessa de Block
- & Octavie Lunguya
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Article
| Open AccessAn innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2
Pathogens often persist within granulomas which form to control infection. Here, Harvest et al describe an innate granuloma that eradicates a ubiquitous environmental pathogen without inducing adaptive immunity.
- Carissa K. Harvest
- , Taylor J. Abele
- & Edward A. Miao
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Article
| Open AccessThe transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells
Type 1 conventional dendritic cells (cDC1) play a pivotal role in the cross-presentation of antigens, enabling efficient CD8 + T cell response. Here authors show that the transcription factor Zeb1 essentially regulates this process via facilitating the reactive-oxygen-species-dependent rupture of phagosomal membrane to allow antigen export to the cytoplasm.
- Yan Wang
- , Quan Zhang
- & Nengming Xiao
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Article
| Open AccessCD8+ T cells control SIV infection using both cytolytic effects and non-cytolytic suppression of virus production
Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects.
- Benjamin B. Policicchio
- , Erwing Fabian Cardozo-Ojeda
- & Ruy M. Ribeiro
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Article
| Open AccessEpidemiology of Plasmodium malariae and Plasmodium ovale spp. in Kinshasa Province, Democratic Republic of Congo
Non-falciparum malaria may cause a significant disease burden in highly endemic regions, but epidemiological data is limited. In this study, the authors estimate the incidence and prevalence of P. malariae, P. ovale spp., in Kinshasa, Democratic Republic of Congo and compare to P. falciparum, which known to be common in the region.
- Rachel Sendor
- , Kristin Banek
- & Jonathan B. Parr
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Article
| Open AccessObesity dysregulates the pulmonary antiviral immune response
Obesity is a risk factor for severe influenza infection. Here, Almond et al show that increased susceptibility is due to increased airway concentrations of the hormone leptin which dampens interferon responses and facilitates severe infection.
- Mark Almond
- , Hugo A. Farne
- & Aran Singanayagam
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Article
| Open AccessCryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry
Here, Ristow et al show that the environmental fungus Cryptococcus adapts to the higher carbon dioxide levels present in human tissue through activation of the Target-of-Rapamycin stress response pathway leading to reorganization of its outer membrane lipids and host adaptation.
- Laura C. Ristow
- , Andrew J. Jezewski
- & Damian J. Krysan
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Article
| Open AccessA spatial sequencing atlas of age-induced changes in the lung during influenza infection
Ageing is known to impair the immune response against infectious pathogens. Here, Kasmani et al. present a spatial and transcriptomic atlas of immune changes in the lungs of young and aged mice in response to influenza virus infection.
- Moujtaba Y. Kasmani
- , Paytsar Topchyan
- & Weiguo Cui
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Article
| Open AccessAssessing the global risk of typhoid outbreaks caused by extensively drug resistant Salmonella Typhi
Extensively drug resistant (XDR) typhoid fever is an emerging global health threat. This study compares data on air travel patterns and typhoid incidence to identify countries at high risk for XDR typhoid outbreaks.
- Joseph Walker
- , Chrispin Chaguza
- & Virginia E. Pitzer
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Article
| Open AccessCryptic susceptibility to penicillin/β-lactamase inhibitor combinations in emerging multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages
Staphylococcus epidermidis can cause invasive infections that are difficult to treat due to multi-resistance to most clinically relevant drugs, including methicillin and other β-lactam antibiotics, vancomycin, and rifampicin. In this work, the authors use in vitro assays and a mouse infection model to explore cryptic susceptibility and development of resistance to penicillin/β-lactamase combinations.
- Xiaoliang Ba
- , Claire L. Raisen
- & Jesper Larsen
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Article
| Open AccessSpatial and temporal dynamics of West Nile virus between Africa and Europe
West Nile virus is an animal pathogen that has spread rapidly in Europe in recent years, causing several human deaths. This study investigates the spatial and temporal dynamics of the virus circulation between Africa (its place of origin) and Europe.
- Giulia Mencattelli
- , Marie Henriette Dior Ndione
- & Giovanni Savini
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Article
| Open AccessExtracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum
Here, Kioko et al. describe a putative posttranscriptional RNA regulation mechanism involving secreted extracellular vesicles to maintain the intracellular steady-state RNA levels during the asexual blood stage of malaria parasites.
- Mwikali Kioko
- , Alena Pance
- & Abdirahman I. Abdi
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Article
| Open AccessStructure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir
In this study, the authors report the structure-based discovery and preclinical evaluation of 2 simnotrelvir, an orally bioavailable 3CLpro inhibitor that blocks replication of SARS-CoV-2 variants in 3 vitro, shows robust efficacy in a mouse model and good safety and pharmacokinetic profiles in rats 4 and monkeys.
- Xiangrui Jiang
- , Haixia Su
- & Yechun Xu
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Article
| Open AccessClinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito
Malaria parasites from patients who fail atovaquone therapies are highly drug-resistant, with mutations at Y268 in cytochrome b. Here the authors show that this mutation results in multiple defects in the parasite’s development and prevents transmission from mosquitoes to mice.
- Victoria A. Balta
- , Deborah Stiffler
- & Theresa A. Shapiro
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Article
| Open AccessPerinatal murine cytomegalovirus infection reshapes the transcriptional profile and functionality of NK cells
Early life infections are known to impact and modulate the immune response in later life. Here the authors show that perinatal infection with murine cytomegalovirus results in a modified transcriptional profile and functionality in murine NK cells.
- Carmen Rožmanić
- , Berislav Lisnić
- & Ilija Brizić
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Article
| Open AccessSARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition
Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.
- Rachel Erickson
- , Chang Huang
- & Peter D. Sun
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Article
| Open AccessDevelopment and validation of the pandemic fatigue scale
In this study the authors introduce a measure of pandemic fatigue and report the existence of, and changes in, pandemic fatigue during the COVID-19 pandemic. They also identify correlates of pandemic fatigue and show that those who experienced more pandemic fatigue were less likely to adhere to various health-protective behaviors.
- Lau Lilleholt
- , Ingo Zettler
- & Robert Böhm
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Article
| Open AccessHIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria
HIV-1 infection is known to impact the gut mucosa, effecting the microbiota and immune system, but early antiretroviral therapy is linked to partial reversal of this phenomena. Here the authors explore the impact of early commencement of antiretroviral therapy and show this can limit the abnormal responses of intestinal B cells associated with HIV-1 infection.
- Cyril Planchais
- , Luis M. Molinos-Albert
- & Hugo Mouquet
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Article
| Open AccessMucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure
HIV-1 can be transmitted by infected cells in body fluids and an efficient prophylaxis should prevent this. Here the authors show that the HIV-1 antibody 10-1074, when applied as topical vaginal gel, inhibits cell-associated transmission in non-human primates.
- Karunasinee Suphaphiphat
- , Delphine Desjardins
- & Mariangela Cavarelli
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Article
| Open AccessSystematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq
Sunshine et al. use Perturb-seq to study host dependencies of SARS-CoV-2 by inactivating host factors genetically and monitoring the course of infection by single-cell sequencing, characterizing global host phenotypes. They identified NFKBIA, EIF4E2 and EIF4H as strong host dependency factors.
- Sara Sunshine
- , Andreas S. Puschnik
- & Marco Y. Hein
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Article
| Open AccessViral kinetics of sequential SARS-CoV-2 infections
In this study, the authors compare the viral kinetics of first and second SARS-CoV-2 infections using data from an occupational surveillance scheme in the National Basketball League. They find that second infections tend to have a faster clearance time, and that clearance times in first and second infections were positively correlated.
- Stephen M. Kissler
- , James A. Hay
- & Yonatan H. Grad
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Article
| Open AccessGlobal burden of disease due to rifampicin-resistant tuberculosis: a mathematical modeling analysis
Rifampicin-resistant tuberculosis (RR-TB) requires longer, more toxic therapy than rifampicin-sensitive disease and is associated with a higher occurrence of long-term sequelae. In this mathematical modeling study, the authors estimate that incident RR-TB in 2020 will be responsible for ~6.9 million disability-adjusted life years; 44% due to post-tuberculosis sequelae.
- Nicolas A. Menzies
- , Brian W. Allwood
- & Ted Cohen
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Article
| Open AccessAlternative splicing in lung influences COVID-19 severity and respiratory diseases
Alternative splicing of transcripts can influence human traits, such as immune response to infection. Here, the authors use mendelian randomization to reveal a role of alternative splicing in lung on COVID-19 severity and susceptibility, offering potential drug discovery avenues.
- Tomoko Nakanishi
- , Julian Willett
- & J. Brent Richards
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Article
| Open AccessGlyco-engineered MDCK cells display preferred receptors of H3N2 influenza absent in eggs used for vaccines
Evolution of human H3N2 influenza has limited the specificity of hemagglutinin to a subset of glycan receptors, which brings challenges. By glyco-engineering cell lines, authors show the importance of extended glycan receptors for growth of recent H3N2 viruses and relevance to their production for vaccines.
- Chika Kikuchi
- , Aristotelis Antonopoulos
- & James C. Paulson
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Perspective
| Open AccessThe uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance
Substandard and falsified medicines are a problem, particularly in low- and middle-income countries, and effects on antimicrobial resistance development aren’t well understood. Here, the authors discuss mechanisms by which they can increase or decrease levels of resistance and the need for improved data collection and analytical approaches.
- Sean Cavany
- , Stella Nanyonga
- & Ben S. Cooper
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Article
| Open AccessNAD+ metabolism is a key modulator of bacterial respiratory epithelial infections
Streptococcus pneumoniae is a common cause of lower respiratory tract infection. Here, Klabunde et al. present a transcriptomic, metabolomic and proteomic characterisation of the bronchial epithelial cell response to infection and show that NAD+ has a role in controlling bacterial replication.
- Björn Klabunde
- , André Wesener
- & Bernd Schmeck
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Article
| Open AccessSelf-sampling monkeypox virus testing in high-risk populations, asymptomatic or with unrecognized Mpox, in Spain
The monkeypox outbreak in 2022 was of global concern. Here the authors present results from an observational study providing self-sampling testing to a high-risk population in a community center in Spain and diagnose monkeypox infection in asymptomatic individuals.
- Cristina Agustí
- , Héctor Martínez-Riveros
- & Jordi Casabona
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Article
| Open AccessEstimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence
The authors used mathematical modeling of human data to study how HIV persists despite suppressive antiretroviral therapy. They found that when latently infected CD4+ T cells proliferate or differentiate, they can create HIV DNA and passage it into other subsets. More mature CD4 cell subsets then clear HIV DNA faster.
- Daniel B. Reeves
- , Charline Bacchus-Souffan
- & Peter W. Hunt
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Article
| Open AccessOmicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease
Here the authors evaluate neutralizing antibodies following COVID-19 bivalent vaccination and find that both Pfizer BA.5 (BNT162b2) and Moderna BA.1 (mRNA-1273) vaccines elicit similar neutralization against Omicron subvariants BA.1, BA.5, BQ.1.1, and XBB.1.5 in patients with end-stage kidney disease.
- Kevin Yau
- , Alexandra Kurtesi
- & Michelle A. Hladunewich
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Article
| Open AccessA Glycolipidated-liposomal peptide vaccine confers long-term mucosal protection against Streptococcus pyogenes via IL-17, macrophages and neutrophils
Vaccines that specifically induce immunity against bacterial pathogens are required. Here the authors produce and characterize an intranasal liposomal vaccine against a peptide antigen from Streptococcus pyogenes and show that it induces a strong mucosal IgA response lasting for over one year, and that protection is dependent on cellular immunity mediated through IL-17, macrophages and neutrophils.
- Victoria Ozberk
- , Mehfuz Zaman
- & Manisha Pandey