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| Open AccessRespiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination
Evidence from animal models suggest a vital role for mucosal vaccination in inducing protection from coronavirus infection. Here the authors examine the B and T cell responses at the lower airways, and contrast humoral and cellular immunity of people after infection and vaccination.
- Elena Mitsi
- , Mariana O. Diniz
- & Daniela M. Ferreira
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| Open AccessFHL1 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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| Open AccessAn 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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| 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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| Open AccessInfection- 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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| 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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| 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
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| Open AccessMonkeypox 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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| Open AccessmRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
The authors report mRNA vaccines encoding a fusion protein of MPXV A35R extracellular domain and full-length M1R and observe improved anti-M1R antibody response. The vaccines show enhanced active and passive protection in female mice challenged with a lethal dose of vaccinia virus.
- Fujun Hou
- , Yuntao Zhang
- & Xiaoming Yang
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| 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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| Open AccessmRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States
Bivalent mRNA COVID-19 vaccines have been developed to provide broader protection against SARS-CoV-2 variants. In this cohort study based on electronic health records from the United States, the authors estimate the effectiveness of bivalent, compared to monovalent, vaccines and no vaccination against a range of COVID-19-related outcomes.
- Hung Fu Tseng
- , Bradley K. Ackerson
- & Lei Qian
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| Open AccessPrevious immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk
In this study, the authors investigate immune responses following a third (booster) SARS-CoV-2 vaccination dose in a cohort of healthcare professionals in Denmark. They find stronger immune responses among those with a prior infection, and correlation between lower antibody responses and higher risk of subsequent breakthrough infection.
- Laura Pérez-Alós
- , Cecilie Bo Hansen
- & Peter Garred
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| Open AccessA Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection
Lassa virus infections in humans can result in severe disease, including hemorrhagic fever. Here the authors describe an mRNA-based Lassa virus vaccine that shows protection without requirement for neutralizing antibody in a guinea pig model of infection.
- Adam J. Ronk
- , Nicole M. Lloyd
- & Alexander Bukreyev
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| Open AccessBenefit-cost analysis of coordinated strategies for control of rabies in Africa
Control of rabies in Africa through mass vaccination of dogs may be compromised by cross-border transmission. Here, the authors use mathematical modelling and a benefit-cost analysis to demonstrate that coordinating rabies control measures across borders could lead to the elimination of dog rabies in Africa.
- A. Bucher
- , A. Dimov
- & J. Zinsstag
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| Open AccessEffect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection
It is unclear whether SARS-CoV-2 immunity decreases transmission through reduction in contagiousness of cases or susceptibility of contacts. Here, the authors use testing and contact data from Geneva, Switzerland and find that increased protection of contacts was the main driver of reduced transmission.
- Denis Mongin
- , Nils Bürgisser
- & Delphine Sophie Courvoisier
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| 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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| Open AccessNeonatal and maternal outcomes following SARS-CoV-2 infection and COVID-19 vaccination: a population-based matched cohort study
The impacts of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy are not fully understood. Here, the authors perform a cohort study using data from Scotland and find that infection was associated with increased risk of preterm birth and some adverse maternal outcomes, but there was no evidence of adverse outcomes associated with vaccination.
- Laura Lindsay
- , Clara Calvert
- & Sarah J. Stock
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| Open AccessEngaging an HIV vaccine target through the acquisition of low B cell affinity
Broadly neutralizing antibodies (bnAbs) for HIV have been difficult to elicit with one issue being the low B cell affinity required. Here the authors use a transgenic mouse bearing human-like antibody repertoires to show that low affinity B cells persist which enables vaccine expansion of antibodies against the CD4 binding site, a conserved HIV bnAb target.
- Larance Ronsard
- , Ashraf S. Yousif
- & Daniel Lingwood
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| Open AccessCharacterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography
Antigenic characterization of new SARS-CoV-2 variants is important to evaluate population immunity and the need for vaccine updates. Here, neutralizing antibodies against newly emerged Omicron variants were analysed in bivalently boosted individuals.
- Annika Rössler
- , Antonia Netzl
- & Janine Kimpel
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| 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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| Open AccessThree-month antibody persistence of a bivalent Omicron-containing booster vaccine against COVID-19
Authors study antibody responses elicited against Omicron BA.1 and variants, by Omicron BA.1-bivalent mRNA-1273.214 vaccine compared with mRNA-1273 vaccination, when administered as a second booster, 90 days post-administration.
- Spyros Chalkias
- , Charles Harper
- & Rituparna Das
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| Open AccessPhase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency
Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.
- Jonas S. Heitmann
- , Claudia Tandler
- & Juliane S. Walz
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| Open AccessEffects of COVID-19 vaccination and previous infection on Omicron SARS-CoV-2 infection and relation with serology
The relative protection against Omicron SARS-CoV-2 infection conferred by vaccination and previous infection are not fully understood. Here, the authors use data from a prospective cohort study in the Netherlands and show that hybrid immunity (vaccination plus previous infection) conferred strongest protection.
- Brechje de Gier
- , Anne J. Huiberts
- & Mirjam J. Knol
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| Open AccessIntradermal 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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| Open AccessSafety and immunogenicity of Ad5-nCoV immunization after three-dose priming with inactivated SARS-CoV-2 vaccine in Chinese adults
Here the authors provide safety and immunogenicity data for an AdV5-based SARS-CoV-2 vaccine, administered intramuscularly as heterologous booster after three-doses of inactivated SARS-CoV-2 vaccine in Chinese adults.
- Hangjie Zhang
- , Nani Xu
- & Huakun Lv
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| 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 AccessCorrelates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2
Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.
- Tomer Hertz
- , Shlomia Levy
- & Orly Weinstein
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| Open AccessAffinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection
Here, the authors use cryo-EM to solve the structures of seven potent human antibodies, and demonstrate in vivo protection in a liver burden assay, using chimeric Plasmodium berghei sporozoites expressing Plasmodium falciparum circumsporozoite protein.
- Gregory M. Martin
- , Jonathan L. Torres
- & Andrew B. Ward
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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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| Open AccessMonoclonal antibody levels and protection from COVID-19
Monoclonal antibodies (mAbs) have shown efficacy against SARS-CoV-2 infection in clinical trials. Here the authors model the dose-response relationship between the dose of mAbs and protection from symptomatic SARS-CoV-2 infection. Further, the protection is comparable to that achieved by vaccination.
- Eva Stadler
- , Martin T. Burgess
- & David S. Khoury
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| Open AccessGeneration of whole tumor cell vaccine for on-demand manipulation of immune responses against cancer under near-infrared laser irradiation
Whole autologous tumor cell vaccine (TCV) has been proposed as a tool for cancer immunotherapy. Here the authors describe the design of a TCV platform based on photothermal nanoparticle-loaded tumor cells, triggering NIR laser irradiation induced anti-tumor immune responses at the vaccination site.
- Jiaqi Meng
- , Yanlin Lv
- & Wei Wei
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| Open AccessEstimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach
Evaluation of the effectiveness of COVID-19 vaccines is increasingly challenging due to high levels of exposure to infection and vaccination. Here, the authors use a model-based approach incorporating these factors and estimate that using a variant-matched rather than ancestral booster could prevent nearly twice as many hospitalisations and deaths over one year.
- Alexandra B. Hogan
- , Patrick Doohan
- & Azra C. Ghani
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| Open AccessHerpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study
The herpes zoster vaccine live was approved in New Zealand in 2018 for use in older adults. This self-controlled case-series study uses whole-country electronic health record data to assess the risk of serious adverse events associated with the vaccine, with results supporting its safety.
- James F. Mbinta
- , Alex X. Wang
- & Colin R. Simpson
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| Open AccessImmunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters
Long-term BA.5-specific efficiency of booster vaccination is incompletely understood. Here, analyzing immunity to and efficacy of various COVID-19 vaccination regimens in Syrian hamster, the authors found that heterologous boosting provides more durable immunity and that NVX-CoV2373 provides the strongest boosting effect.
- Rafael R. G. Machado
- , Jordyn L. Walker
- & Scott C. Weaver
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| Open AccessWaning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination
Efficiency of SARS-CoV-2 vaccines has long been attributed to the neutralising capacity of the antibodies that are produced upon prime-boost vaccinations. Here authors show that upon vaccination with CoronaVac and BNT162b2 vaccines in prime-boost regimens, antibodies with Fc-effector functions to enhance cellular and innate immunity are also produced, albeit with different kinetics.
- X. Tong
- , R. P. McNamara
- & R. A. Medina
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| Open AccessIntranasal 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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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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| Open AccessBias assessment of a test-negative design study of COVID-19 vaccine effectiveness used in national policymaking
Test-negative case control studies have been widely used to estimate COVID-19 vaccine effectiveness, but the accuracy of estimates may be impacted by bias and unmeasured confounding. Here, the authors investigate the these impacts by collecting additional data from individuals included in the first UK COVID-19 test negative study.
- Sophie Graham
- , Elise Tessier
- & Helen I. McDonald
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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 AccessIncreased vaccine sensitivity of an emerging SARS-CoV-2 variant
The SARS-CoV-2 Omicron lineage XBB/XBB.1.5 became the leading cause of new infections in the US in January 2023. Here, the authors use testing and hospitalisation data and show that this variant has increased ability to evade infection-derived immunity but enhanced vaccine sensitivity.
- Joseph A. Lewnard
- , Vennis Hong
- & Sara Y. Tartof
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| Open AccessAge-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade
Age-associated B cells (ABC) have been shown to be associated with autoimmunity and ageing. Here the authors examine whether ABC are transcriptionally or functionally altered in participants with reduced immune cell function and show that, being transcriptionally similar, high pre-vaccine levels are associated with poor vaccine response.
- Juan Carlos Yam-Puc
- , Zhaleh Hosseini
- & James E. D. Thaventhiran
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Article
| Open AccessCampylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques
Utilising various Campylobacter vaccination regimens, the authors explore the effect of vaccination on Campylobacter-associated diarrhoea, mortality, and growth kinetics in vaccinated infant rhesus macaques.
- Sara M. Hendrickson
- , Archana Thomas
- & Mark K. Slifka
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Article
| Open AccessGenomic epidemiology of Vibrio cholerae during a mass vaccination campaign of displaced communities in Bangladesh
The Cox’s Bazar area of Bangladesh has received a large number of Forcibly Displaced Myanmar Nationals. Cholera outbreaks have been detected in the area, and here, the authors perform genomic surveillance of cholera in the refugee and non-refugee population to infer the risk of epidemic spread.
- Alyce Taylor-Brown
- , Mokibul Hassan Afrad
- & Firdausi Qadri
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Article
| Open AccessUnmodified rabies mRNA vaccine elicits high cross-neutralizing antibody titers and diverse B cell memory responses
Here the authors show that in non-human primates two doses of an mRNA-based rabies vaccine induce higher levels of vaccine-specific B cells and cross-neutralizing antibodies compared to two doses of a licensed whole inactivated virus vaccine.
- Fredrika Hellgren
- , Alberto Cagigi
- & Karin Loré
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Article
| Open AccessSafety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis
Here the authors report initial findings of a phase 1 clinical trial, showing that an investigational, mRNA-based vaccine for seasonal influenza (mRNA-1010) has no safety concerns and produces immune responses in adults that are similar or higher than a licensed comparator vaccine.
- Ivan T. Lee
- , Raffael Nachbagauer
- & Robert Paris
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Article
| Open AccessExamining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration
Here the authors assess neutralizing antibody (nAb) levels as correlate of protection in a monoclonal antibody prevention trial and a vaccine trial for COVID-19 and show that nAb titers correlate with clinical protection against COVID-19 supporting nAb titer as a surrogate endpoint for authorization of monoclonal antibodies.
- Dean Follmann
- , Meagan P. O’Brien
- & Myron S. Cohen
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Article
| Open AccessVaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response
Protective immunity against SARS-CoV-2 relies on both antibodies and a T cell dependent response, however, direct experimental evidence for the contribution of cellular immunity is limited. Here authors present a mouse model that is susceptible to SARS-CoV-2 and lacks B cells to demonstrate the emergence of efficient cellular immune response against SARS-CoV-2 upon vaccination or viral challenge.
- Xiaolei Wang
- , Terrence Tsz-Tai Yuen
- & Jian-Dong Huang
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Article
| Open AccessIntranasal 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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Article
| Open AccessEstimating the impact of COVID-19 vaccine inequities: a modeling study
Global COVID-19 vaccine distribution has been inequitable. In this mathematical modelling study, the authors estimate the proportion of deaths that could have been averted in twenty low- and lower-middle-income countries if vaccines had been more widely available early in the pandemic.
- Nicolò Gozzi
- , Matteo Chinazzi
- & Alessandro Vespignani