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| Open AccessEffectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel
Data on the effectiveness of a third dose of COVID-19 vaccine in pregnant women are limited. In this observational study, the authors report that a third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy enhances protection against maternal adverse COVID-19-related outcomes.
- Joshua Guedalia
- , Michal Lipschuetz
- & Ofer Beharier
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Article
| Open AccessThird primary SARS-CoV-2 mRNA vaccines enhance antibody responses in most patients with haematological malignancies
SARS-CoV-2 vaccination has shown reduced efficacy in patients with haematological malignancies. Here, the authors show that a third vaccine is able to enhance SARS-CoV-2 antibody responses in most cases in a cohort of 381 patients with haematological malignancies.
- Lucy B. Cook
- , Gillian O’Dell
- & Andrew J. Innes
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Article
| Open AccessSafety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents
Few countries have approved SARS-CoV-2 booster doses in children and adolescents due to insufficient evidence about the safety and interval vaccination. Here, the authors assess the safety and immunogenicity of a homologous booster dose of CoronaVac in a cohort of 3–17 year olds.
- Lei Wang
- , Zhiwei Wu
- & Qiang Gao
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Article
| Open AccessDurability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19
Here, the authors report results from a Phase 1 trial with an AS03-adjuvanted, plant-based virus-like particle displaying the spike protein of the ancestral SARS-CoV-2. Six months post-second dose, they observe good neutralizing antibody titers and T cell responses to ancestral virus and variants of concern in participants.
- Philipe Gobeil
- , Stéphane Pillet
- & Brian J. Ward
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| Open AccessDistinct immunological and molecular signatures underpinning influenza vaccine responsiveness in the elderly
Seasonal influenza vaccination is an important strategy to prevent serious disease in the elderly, but individual responsiveness to vaccination widely vary. Here authors establish, with an array of state-of-the art methods, the major immunological parameters that distinguish vaccine recipients developing robust antibody response and non-responders
- Peggy Riese
- , Stephanie Trittel
- & Carlos A. Guzmán
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Article
| Open AccessA fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain
Despite the availability of booster doses against SARS-CoV-2, variants of concern are capable of escaping immune responses established by vaccination or natural infection. In this work, the authors detail the immune responses elicited in a cohort of healthcare workers, receiving a fourth dose of inactivated vaccine.
- Ji Wang
- , Caiguangxi Deng
- & Haipeng Xiao
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Article
| Open AccessIntranasal 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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Article
| Open AccessViral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection
COVID vaccination can reduce virus levels in breakthrough infections, which in turn may reduce transmission of the virus. By using qRT-PCR cycle threshold as a surrogate of virus levels, the authors here show that this positive effect of vaccination wanes relatively quickly for Omicron breakthrough infection.
- Yonatan Woodbridge
- , Sharon Amit
- & Naama M. Kopelman
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Article
| Open AccessUpdated 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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| Open AccessAnalysis of anti-SARS-CoV-2 Omicron-neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources
Although COVID-19 convalescent plasma is commonly used for the treatment of immunosuppressed patients, this approach has yielded mixed results. Here, the authors present a systematic review of Omicron-neutralization data in convalescent plasma from vaccinated and unvaccinated individuals.
- David J. Sullivan
- , Massimo Franchini
- & Daniele Focosi
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Article
| Open AccessDynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack
The membrane-proximal external region of HIV-1 spike protein is a broadly neutralizing antibody target. Here, cryo-electron microscopy and molecular dynamics reveal spontaneous ectodomain tilting, a vulnerability exploitable for vaccine design.
- Shuang Yang
- , Giorgos Hiotis
- & Thomas Walz
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Article
| Open AccessBreadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine
The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.
- Dapeng Li
- , David R. Martinez
- & Barton F. Haynes
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| Open AccessPriming conditions shape breadth of neutralizing antibody responses to sarbecoviruses
Vaccination and infection history determine the breadth of neutralizing antibody response to SARS-CoV-2 variants and other sarbecoviruses with breakthrough or natural infection combined with vaccination or booster vaccination with mRNA vaccine providing highest neutralization.
- Janice Zhirong Jia
- , Chee Wah Tan
- & Sophie A. Valkenburg
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Article
| Open AccessHIV-1 CD4-binding site germline antibody–Env structures inform vaccine design
VRC01-class bNAbs against the CD4 binding site of HIV-1 Env are targets of vaccine design. Here, the authors structurally characterized germline versions of the VRC01-class bNAb, BG24, bound to Env. They reveal mechanisms of germline binding, informing the design of VRC01-class targeting immunogens.
- Kim-Marie A. Dam
- , Christopher O. Barnes
- & Pamela J. Bjorkman
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| Open AccessSARS-COV-2 antibody responses to AZD1222 vaccination in West Africa
Data on immune response to the SARS-COV-2 AZD1222 vaccine are limited in African populations. Here, the authors show immunogenicity of the AZD1222 vaccine in two independent cohorts from West Africa, including seroprevalence levels prior to vaccine rollout in January 2021.
- Adam Abdullahi
- , David Oladele
- & Ravindra K. Gupta
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Article
| Open AccessChAd155-RSV vaccine is immunogenic and efficacious against bovine RSV infection-induced disease in young calves
A pediatric RSV vaccine is an unmet medical need, even after >50 years of effort. Here, the authors show that a chimpanzee adenovirus based RSV vaccine candidate protects calves from disease upon RSV infection, regardless of the time after vaccination (1 or 4 months) or the presence of maternal antibodies.
- Rineke de Jong
- , Norbert Stockhofe-Zurwieden
- & Ann-Muriel Steff
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| Open AccessImmunopeptidomics-based design of mRNA vaccine formulations against Listeria monocytogenes
Currently, no approved vaccines for Listeria monocytogenes are available. Here, the authors use immunopeptidomics to map bacterial peptides presented on infected cells and identify antigens that, as mRNA vaccine, provide protection in mice.
- Rupert L. Mayer
- , Rein Verbeke
- & Francis Impens
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Article
| Open AccessEffectiveness of an inactivated Covid-19 vaccine with homologous and heterologous boosters against Omicron in Brazil
This study investigates the effectiveness of COVID-19 vaccine boosters following a primary series of CoronaVac vaccination. Using data from Brazil during the Omicron wave, the authors show that boosters provided protection against severe disease, with higher effectiveness from a BNT162b2 than CoronaVac booster.
- Otavio T. Ranzani
- , Matt D. T. Hitchings
- & Julio Croda
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Article
| Open AccessNeutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion
The Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1) is a prime vaccine candidate for malaria. Here, the authors structurally and functionally characterise a panel of naturally acquired MSP-1 specific antibodies to identify one with potent broadly neutralising activity and better understand immune evasion mechanisms.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
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Article
| Open AccessImmunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients
Characterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease.
- Clovis A. Silva
- , Ana C. Medeiros-Ribeiro
- & Eloisa Bonfa
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Comment
| Open AccessThe potential of Beta variant containing COVID booster vaccines for chasing Omicron in 2022
Currently approved COVID vaccines are designed using the spike antigen derived from the ancestral strain, but health authorities are recommending changes to the vaccine strain to combat emerging variants. The goal is to ensure that next generation vaccines can tackle multiple variants of concern including the most prevalent variant for the coming season. We here discuss recent preclinical and clinical data on COVID vaccine antigens that are potential candidates for an updated vaccine.
- Saranya Sridhar
- , Roman M. Chicz
- & Jean-Francois Toussaint
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| Open AccessSpike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study
Vaccination can provide reliable and long-lasting protection against COVID-19, however the immune response to vaccination can vary between individuals and can decline over time, leading to differences in protective effects. Here the authors assess the immune response to COVID-19 vaccination across a large cohort of previously uninfected adults and demonstrate lower post-vaccination antibody levels amongst those with immune-suppressing conditions and medications, as well as those with several other more common chronic conditions.
- Madhumita Shrotri
- , Ellen Fragaszy
- & Robert W. Aldridge
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Article
| Open AccessEffectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study
SARS-CoV-2 variants of concern have been associated with reduced vaccine effectiveness, even after a booster dose. In this study, authors aim to estimate vaccine effectiveness against hospitalisation with the Omicron and Delta variants, using different definitions of hospitalisation in secondary care data.
- Julia Stowe
- , Nick Andrews
- & Jamie Lopez Bernal
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| Open AccessStructure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies
Pfs48/45, a surface protein of Plasmodium falciparum, is a promising anti-malarial vaccine candidate whose structure is not entirely resolved. Here, the authors present the structure of the full-length molecule, and characterise the binding and activity of transmission blocking antibodies.
- Kuang-Ting Ko
- , Frank Lennartz
- & Matthew K. Higgins
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Article
| Open AccessA self-assembled trimeric protein vaccine induces protective immunity against Omicron variant
The SARS-CoV-2 Omicron variant has quickly become the predominant circulating variant, due to the high transmissibility and immune escape. Here, the authors develop a trimeric protein vaccine candidate and show a sustained humoral immune response, and protection from challenge (Omicron and Delta) in various animal models.
- Cai He
- , Jingyun Yang
- & Xiawei Wei
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Article
| Open AccessA randomized controlled trial of heterologous ChAdOx1 nCoV-19 and recombinant subunit vaccine MVC-COV1901 against COVID-19
Public safety concern of the ChAdOx1 vaccine has led to an alternative immunisation strategy against SARS-CoV-2, with this heterologous schedule widely adopted and officially recommended in many countries. Here, the authors report the immunogenicity and safety outcomes of heterologous prime-boost immunisation with ChAdOx1 and a spike-2P subunit vaccine in a single-blinded, randomised trial.
- Chih-Jung Chen
- , Lan-Yan Yang
- & Kuan-Ying A. Huang
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| Open AccessHeterologous vector versus homologous mRNA COVID-19 booster vaccination in non-seroconverted immunosuppressed patients: a randomized controlled trial
Optimizing COVID-19 vaccination strategies for patients under immunosuppressive medication is of high importance. In this clinical trial including non-seroconverted immunosuppressed patients, a homologous mRNA booster vaccination resulted in higher seroconversion rate than a switch to a vector-based vaccine.
- Daniel Mrak
- , Daniela Sieghart
- & Michael Bonelli
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Article
| Open AccessNETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia
The mechanisms underlying the pathogenesis of vaccine-induced immune thrombotic thrombocytopenia (VITT) remain unclear. Here the authors show that anti-PF4 antibodies are responsible for the activation of platelets and neutrophils, and blockage of FcγRIIa or NETosis in vivo can prevent thrombosis.
- Halina H. L. Leung
- , Jose Perdomo
- & Beng H. Chong
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Article
| Open AccessNeutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen
The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.
- Ayaka Washizaki
- , Asako Murayama
- & Takanobu Kato
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Article
| Open AccessSARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals
Prior exposure to infectious agents can impact the vaccination induced immune response. Here the authors show prior SARS-CoV-2 infection results in more efficient induction of mucosal SARS-CoV-2 secretory IgA antibody following mRNA vaccination.
- Kaori Sano
- , Disha Bhavsar
- & Florian Krammer
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Comment
| Open AccessCall for a unified approach to Monkeypox infection in pregnancy: Lessons from the COVID-19 pandemic
In the current monkeypox outbreak, vaccination and treatment of pregnant women are recommended only if the benefits outweigh risks, but the extremely sparse data available limit evidence-based recommendations. We must facilitate a unified consensus approach to rapidly collect robust data. Two years into the COVID-19 pandemic, monkeypox has emerged as yet another challenge to the mother-fetus dyad, potentially placing both at risk, if exposed.
- Asma Khalil
- , Athina Samara
- & Shamez Ladhani
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Article
| Open AccessImmunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV
HIV infection may affect the immune response to vaccination. Here the authors show that humoral response in persons living with HIV after the third dose of a SARS-CoV-2 vaccine is strong and higher than that achieved with the second dose, while cell-mediated immunity remains stable.
- Alessandra Vergori
- , Alessandro Cozzi Lepri
- & Eleonora Tartaglia
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| Open AccessSARS CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T-cells
Here, the authors show in a cohort of people with HIV, COVID mRNA vaccination is followed by a transient boost in a particular profile of HIV-specific T-cell responses and a corresponding decrease in residual HIV RNA – suggesting productive immune engagement with infected cells.
- Eva M. Stevenson
- , Sandra Terry
- & R. Brad Jones
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Article
| Open AccessSARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort
Here the authors provide data from a sub-cohort of the Virus Watch study (19,556 adults) who completed at-home capillary blood sampling on a monthly basis and describe an association between anti-spike antibody levels and risk of SARS-CoV-2 infection.
- Robert W. Aldridge
- , Alexei Yavlinsky
- & Andrew Hayward
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Article
| Open AccessBNT162b2-boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19
Vaccines against SARS-CoV-2 have changed the course of the COVID-19 pandemics, but waning immunity necessitates repeated immunization. Authors here show that immunity declines faster following two doses of vector-based vaccine compared to a first dose of vector-based vaccine followed by boosting with an mRNA vaccine, but application of an mRNA vaccine as a third dose minimises the difference between the two groups.
- Georg M. N. Behrens
- , Joana Barros-Martins
- & Reinhold Förster
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Article
| Open AccessPromotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein
Protection against SARS-CoV-2 infection involves T cell and B cell responses but only studying one or the other has proved difficult. Here the authors immunise with a fusion protein construct of N and RBD proteins from SARS-CoV-2 and find that this promotes protection in animal models preferentially via T cells.
- Julia T. Castro
- , Patrick Azevedo
- & Ricardo T. Gazzinelli
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Article
| Open AccessSecond-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland
Here, Simpson et al. analyze data from 3.6 million COVID-19 vaccine second doses (ChAdOx1 and BNT162b2) in Scotland for risk of thrombocytopenic, thromboembolic and hemorrhagic events. Borderline increased risks of immune thrombocytopenic purpura and cerebral venous sinus thrombosis were found for the ChAdOx1 vaccine. These events were rare and usually short-lived.
- Colin R. Simpson
- , Steven Kerr
- & Aziz Sheikh
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Article
| Open AccessProtection of COVID-19 vaccination and previous infection against Omicron BA.1, BA.2 and Delta SARS-CoV-2 infections
The protection of COVID-19 vaccines against emerging variants needs to be monitored. Here, the authors use community testing data from the Netherlands and find that protection against infection by Omicron subvariants BA.1 and 2 is low and that booster vaccines considerably but temporarily increase protection.
- Stijn P. Andeweg
- , Brechje de Gier
- & Mirjam J. Knol
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Article
| Open AccessComparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens
Multiple formulations and technologies for vaccinating against SARS-CoV-2 exist but how the use of these in homologous or heterologous format impacts immunogenicity is far from clear. Here the authors compare a range of heterologous and homologous SARS-CoV-2 vaccination strategies and assess the induced humoral and cellular immune response.
- Verena Klemis
- , Tina Schmidt
- & Martina Sester
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Article
| Open AccessDevelopment of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses
The public health concern caused by influenza B virus is often overlooked, yet represents a significant global burden. Here, the authors evaluate the cellular and humoral immune responses of multivalent vaccine candidates, based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA platform, and demonstrate protection of mice from challenge with a broad panel of influenza B viruses.
- Norbert Pardi
- , Juan Manuel Carreño
- & Meagan McMahon
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Article
| Open AccessChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants
Whilst the ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated efficacy against symptomatic disease, variants of concern (VOCs) with spike protein substitutions have led researchers to explore updating vaccines from ancestral spike protein. Authors use a Syrian hamster model to evaluate a vaccine encoding the spike protein of Beta VOC and assess efficacy against VOCs.
- Neeltje van Doremalen
- , Jonathan E. Schulz
- & Vincent J. Munster
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Article
| Open AccessAntibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination
Here the authors show that a third SARS-CoV-2 vaccination significantly boosts neutralizing antibodies against Omicron subvariants and that hybrid immunity (infection and vaccination) results in broader neutralization activity and cross-reactive antibody affinity maturation.
- Lorenza Bellusci
- , Gabrielle Grubbs
- & Surender Khurana
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Article
| Open AccessLower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose
Responses to SARS-CoV-2 vaccines in different populations are important to define efficacy. Here the authors show using a cohort in Singapore that two doses of mRNA vaccine is less effective in recipients over 60 years of age and that a further dose of vaccine can improve these antibody levels.
- Laurent Renia
- , Yun Shan Goh
- & Lisa F. P. Ng
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Article
| Open AccessCOVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation
Vaccines induce beneficial immunity for COVID-19, but immune waning prompts boosting vaccination. Here, the authors show that a third, boosting dose of COVID-19 mRNA vaccine induces transient CD8 + T effector cell response while conserving the CD8 memory T cell pool, thereby permitting reactivation of spike-specific CD8 + T cells upon breakthrough infection or 4th vaccination.
- Matthias Reinscheid
- , Hendrik Luxenburger
- & Maike Hofmann
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Article
| Open AccessA public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike
To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.
- Mathieu Claireaux
- , Tom G. Caniels
- & Marit J. van Gils
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Article
| Open AccessCAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns
Respiratory syncytial virus is a major pathogen with burden observed and associated with childhood infection. Here the authors characterise a cationic adjuvant formulation and show single immunisation results in protection in a murine neonate model of respiratory syncytial virus infection.
- Simon D. van Haren
- , Gabriel K. Pedersen
- & Ofer Levy
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Article
| Open AccessEvaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy
Pregnant individuals are at higher risk of SARS-CoV-2-related morbidity and mortality, yet more studies are needed to evaluate safety and efficacy of vaccination during pregnancy, and also the level of protection provided to the newborn. Here, the authors evaluate transplacental transfer of mRNA vaccine products and functional SARS-CoV-2 antibodies during pregnancy and early infancy.
- Mary Prahl
- , Yarden Golan
- & Stephanie L. Gaw
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Article
| Open AccessA 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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Article
| Open AccessDifferential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines
Emerging SARS-CoV-2 variants raise concerns on immune evasion. Here, the authors evaluate the neutralization efficiency of COVID-19 mRNA vaccinee sera against representative viruses of 13 WHO-designated SARS-CoV-2 variants of concern/interest.
- Li Wang
- , Markus H. Kainulainen
- & Bin Zhou