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| 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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| 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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| 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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| 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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| 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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| 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
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| Open AccessGRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults
Palmer et al. present interim findings from their clinical trial; they describe the reactogenicity and immunogenicity results of a self-amplifying mRNA SARS-CoV-2 booster vaccine within an older population (≥60 years of age).
- Christine D. Palmer
- , Ciaran D. Scallan
- & Andrew Ustianowski
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| Open AccessAn mRNA-based T-cell-inducing antigen strengthens COVID-19 vaccine against SARS-CoV-2 variants
The authors show that an mRNA-based T-cell-inducing antigen combined with the receptor-binding domain of the SARS-CoV-2 spike protein strengthens the COVID19 vaccine against SARS-CoV-2 variants, suggesting improved vaccine designs that comprehensively stimulate both humoral and cellular responses.
- Wanbo Tai
- , Shengyong Feng
- & Gong Cheng
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| Open AccesssaRNA vaccine expressing membrane-anchored RBD elicits broad and durable immunity against SARS-CoV-2 variants of concern
Vaccines with broad and long-lasting protection against variants of concern are still limited. Here, the authors report a self-amplifying RNA (saRNA) vaccine expressing a membrane-anchored SARS-CoV-2 Spike RBD and show that it elicits broad, durable and protective immunity in small animal models and NHPs.
- Mai Komori
- , Takuto Nogimori
- & Wataru Akahata
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Article
| Open AccessStructural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage
In this study, Henderson and Zhou et al. visualize the development of a HIV-1 broadly neutralizing antibody (bnAb) from germline to maturity by determining cryo-EM structures of HIV-1 Envelope (Env) proteins bound to Fab fragments of antibodies at different stages of development of a Env V3-glcyan supersite targeting bnAb clone.
- Rory Henderson
- , Ye Zhou
- & Priyamvada Acharya
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Article
| Open AccessCap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures
Removing immunogenic uncapped mRNA from transcribed mRNA can be challenging, but is critical in mRNA research and clinical applications such as vaccines. Here, authors develop hydrophobic photocaged tag-modified cap analogs, which can be used to separate capped mRNA from uncapped mRNA, with subsequent tag removal using photo-irradiation.
- Masahito Inagaki
- , Naoko Abe
- & Hiroshi Abe
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| Open AccessCationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants
Lei et al. show that intranasal immunisation with their vaccine candidate is able to broadly protect mice from SARS-CoV-2 infection, including Omicron variants.
- Hong Lei
- , Aqu Alu
- & Xiawei Wei
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| Open AccessThe impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria
Nigeria has the highest incidence of pneumococcal disease in Africa and introduced the 10-valent pneumococcal vaccine for infants between 2014 and 2016. Here, the authors conduct repeated cross-sectional surveys to analyse the impact of the vaccination campaign on pneumococcal carriage and serotype distribution.
- Aishatu L. Adamu
- , J. Ojal
- & Ifedayo M. O. Adetifa
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| Open AccessImmunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice
In this study, the authors provide pre-clinical evaluation of immunogenicity of the “ChulaCov19” mRNA vaccine encoding the ectodomain of the SARS-CoV-2 S protein. The vaccine induced potent immune response when applied as homologous prime/boost immunization or as heterologous booster and protected mice from disease.
- Eakachai Prompetchara
- , Chutitorn Ketloy
- & Kiat Ruxrungtham
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Article
| Open AccessInactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants
In this study, the authors isolate and characterize BBIBPCorV inactivated vaccine-elicited human antibodies. They show that these can broadly neutralize a range of SARS-CoV-2 variants and protect mice from Delta and Omicron infection. The neutralization mechanism of bispecific antibodies were solved structurally.
- Yubin Liu
- , Ziyi Wang
- & Gong Cheng
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| Open AccessA ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates
Here the authors develop a ferritin-based protein nanoparticle vaccine candidate for SARS-CoV-2, and show induction of neutralizing antibodies to variants of concern, including Omicron BQ.1, in non-human primates after initial immunization and a booster dose.
- Payton A.-B. Weidenbacher
- , Mrinmoy Sanyal
- & Peter S. Kim
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| Open AccessAn 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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| Open AccessEffectiveness of inactivated COVID-19 vaccines among older adults in Shanghai: retrospective cohort study
Inactivated COVID-19 vaccines have been widely used in China, but there is limited real-world evidence for their effectiveness in this setting. Here, the authors estimate effectiveness of inactivated vaccines for people aged 60 or older in Shanghai during a period when Omicron was the dominant circulating variant.
- Zhuoying Huang
- , Shuangfei Xu
- & Weibing Wang
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| Open AccessSingle-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates
Here the authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.
- Yi-Nan Zhang
- , Jennifer Paynter
- & Jiang Zhu
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| Open AccessBooster with Ad26.COV2.S or Omicron-adapted vaccine enhanced immunity and efficacy against SARS-CoV-2 Omicron in macaques
Variant booster vaccines are a strategy to improve protection against SARS-CoV-2. Here, the authors find that both Wuhan-Hu-1-based Ad26.COV2.S or an Omicron-adapted booster vaccine provide robust immune responses and protection against Omicron in NHP.
- Laura Solforosi
- , Lea M. M. Costes
- & Frank Wegmann
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| Open AccessLimited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection
Resident memory T cells at the respiratory tract may play critical roles in the response to respiratory infections including SARS-CoV-2. Here the authors characterise the lung resident T cell response generated in response to mRNA vaccination of SARS-CoV-2 Spike or in convalescent patients after natural infection. They show reduced frequency and functionality of tissue resident T cells in vaccinated versus convalescent patients which may impact disease control and vaccination strategies.
- Daan K. J. Pieren
- , Sebastián G. Kuguel
- & Meritxell Genescà
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| Open AccessEffectiveness of BNT162b2 after extending the primary series dosing interval in children and adolescents aged 5–17
Extending the interval between doses of mRNA Covid-19 vaccines has been linked with a reduced risk of myocarditis in children and adolescents, but impacts on vaccine effectiveness are not known. Here, the authors perform a nested case-control study using data from Hong Kong and find evidence of reduced risk of infection following a longer dosing interval.
- Francisco Tsz Tsun Lai
- , Min Fan
- & Esther Wai Yin Chan
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| Open AccessCommercial influenza vaccines vary in HA-complex structure and in induction of cross-reactive HA antibodies
Here, Myers and Gallagher et al. characterize the structural organization of commercial influenza vaccines. The vaccines differ in their structural composition and identify a “spiked nanodisc” arrangement of hemagglutinin (HA) with increased display and immunogenicity of the conserved stem region of HA.
- Mallory L. Myers
- , John R. Gallagher
- & Audray K. Harris
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| Open AccessLong-term measles antibody profiles following different vaccine schedules in China, a longitudinal study
The timing of measles vaccination in infants affects the risk of infection in young children and the duration of protection provided. Here, the authors investigate optimal vaccination timing by characterising antibody kinetics following different vaccine schedules in two cohorts of children in southern China.
- Qianli Wang
- , Wei Wang
- & Hongjie Yu
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| Open AccessmRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5
Omicron strains of SARS-CoV-2 have displayed high transmissibility and immunological escape to antibody responses derived from natural infection and vaccination. Here the authors compare the antibody response to vaccination and natural infection, assessing neutralisation after vaccine doses and analyse the repertoire of such responses.
- Emanuele Andreano
- , Ida Paciello
- & Rino Rappuoli
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| Open AccessRisk of death following COVID-19 vaccination or positive SARS-CoV-2 test in young people in England
Rare but serious cardiac disease side effects have been linked to COVID-19 vaccinations, especially in young people. Here, the authors find very little evidence of an association between vaccination and mortality, except for in females after a non mRNA vaccine, but show an increased risk of death following COVID-19 infection
- Vahé Nafilyan
- , Charlotte R. Bermingham
- & James C. Doidge
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| Open AccessPredicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis
In this study, the authors perform a meta-analysis of COVID-19 vaccine effectiveness studies and compare observed protection against severe disease with model-based estimates of neutralising antibody titres. Their results show that SARS-CoV-2 antibody titres are predictive of protection against severe COVID-19 disease.
- Deborah Cromer
- , Megan Steain
- & Miles P. Davenport
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| Open AccessCorrelates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers
Correlation between vaccine induced serological response and protection against SARS-CoV-2 omicron infection is not well understood. Authors investigate breakthrough infections in triple-vaccinated healthcare workers, to characterise correlates of protection and viral characteristics.
- Ulrika Marking
- , Sebastian Havervall
- & Charlotte Thålin
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Article
| Open AccessHeterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain
Takano et al. show that heterologous booster by SARS-CoV-2 recombinant spike protein vaccine recalls a more sustained and broader anti-spike receptor-binding domain antibody response compared to homologous booster by mRNA vaccine.
- Tomohiro Takano
- , Takashi Sato
- & Yoshimasa Takahashi
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| Open AccessA 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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| Open AccessRapid 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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| Open AccessBeta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates
Waning protective efficacy of mRNA-based booster vaccinations has been observed against newly emerging SARS-CoV-2 variants of concern. In this work, Pavot et al. formulate a monovalent Beta vaccine and demonstrate durable cross-neutralising antibody responses in non-human primates, against a spectrum of variants.
- Vincent Pavot
- , Catherine Berry
- & Valerie Lecouturier
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| Open AccessSARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity
Whilst SARS-CoV-2 mRNA vaccines have demonstrated efficacy in reducing infection severity, research has shown that SARS-CoV-2 infection is associated with new autoantibodies. Whether this would also be observed during mRNA vaccination is unclear. Here, the authors use an autoantibody screening platform to monitor autoantibody responses in a diverse cohort during vaccination.
- Jillian R. Jaycox
- , Carolina Lucas
- & Aaron M. Ring
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| Open AccessDirect 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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| Open AccessEffectiveness of mRNA COVID-19 vaccine booster doses against Omicron severe outcomes
This study investigates the protection provided by mRNA COVID-19 vaccine booster doses against Omicron-associated severe disease in adults aged 50 and older. The authors use data from Ontario, Canada, and find that booster doses provide strong protection but that it declined during the period of BA.4/BA.5 predominance.
- Ramandip Grewal
- , Lena Nguyen
- & Jeffrey C. Kwong
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| Open AccessSafety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults
Here the authors present results from a randomized, double-blinded Phase 1 clinical trial, testing a thermostable presentation of a clinical-stage adjuvanted subunit tuberculosis vaccine candidate. The vaccine candidate is safe and well tolerated, and elicits comparable or improved immune responses compared to the non-thermostable presentation.
- Zachary K. Sagawa
- , Cristina Goman
- & Christopher B. Fox
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Article
| Open AccessImmunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants
Current SARS-CoV-2 variants evade immune responses induced by approved vaccines. In this study, the authors find that a recombinant prefusion-stabilized Beta spike protein vaccine confers broad neutralization capacity in mice and non-human primates as well as protective antibody and immune memory responses.
- James Logue
- , Robert M. Johnson
- & Matthew B. Frieman
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Article
| Open AccessEngineering 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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Article
| Open AccessMaternal SARS-CoV-2 vaccination and infant protection against SARS-CoV-2 during the first six months of life
This study investigates the impact of maternal COVID-19 vaccination during pregnancy on infant infection during the first six months of life. Using data from California, USA, the authors find that protection against infection during the period of Delta dominance was high, but that it declined during the Omicron period.
- Ousseny Zerbo
- , G. Thomas Ray
- & Nicola P. Klein
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Article
| Open AccessSomatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants
In this study, authors identified neutralizing antibodies by isolating B cells from SARS-CoV-2 Delta infected patients and detect altered structural features, likely introduced by somatic hypermutation, that are involved in epitope binding and increase neutralization breadth against virus variants.
- Haisheng Yu
- , Banghui Liu
- & Xiaoping Tang
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Article
| Open AccessThe cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
A gB/MF59 vaccine candidate for human cytomegalovirus (HCMV) provided partial protection in organ transplant patients. Here, the authors identify antibody responses in trial participants that target virally infected cells to control cell-to-cell spread of HCMV, providing a potential mechanism for the observed protection.
- A. C. Gomes
- , I. A. Baraniak
- & M. B. Reeves
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Article
| Open AccessNational surveillance data analysis of COVID-19 vaccine uptake in England by women of reproductive age
Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England.
- Laura A. Magee
- , Erika Molteni
- & Sara White
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Article
| Open AccessOptimal age targeting for pneumococcal vaccination in older adults; a modelling study
Vaccination against invasive pneumococcal disease is recommended for older adults but the optimal age group to target has not been determined and may vary by epidemiological setting. Here, the authors use statistical modelling to estimate the optimal ages for vaccination in Brazil, England, Malawi, and South Africa.
- Deus Thindwa
- , Samuel Clifford
- & Stefan Flasche
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Article
| Open AccessEfficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models
Here the authors show efficacy of a low-dose, unmodified, bivalent mRNA vaccine against SARS-CoV-2 variants in two female rodent models and find that combination of mRNA encoding Beta and Delta Spike sequences induces broadly neutralizing antibodies and robust T-cell responses.
- Björn Corleis
- , Donata Hoffmann
- & Anca Dorhoi
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Article
| Open AccessThe impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England
In England, SARS-CoV-2 vaccines were initially targeted to older, more vulnerable people; first vaccine doses were prioritised over second doses, and an interval of twelve weeks was used between doses. Here, the authors assess the impacts of these policy decisions by simulating counterfactual scenarios.
- Matt J. Keeling
- , Samuel Moore
- & Edward M. Hill
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Article
| Open AccessHIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14+ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.
- Massimiliano Bissa
- , Sohyoung Kim
- & Genoveffa Franchini
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Article
| Open AccessA modular vaccine platform enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens
Antigen display on outer membrane vesicles (OMVs) can be difficult to control and highly variable. Here, the authors describe a universal approach called AvidVax for linking biotinylated antigens to the exterior of OMVs and enabling rapid vaccine assembly.
- Kevin B. Weyant
- , Ayomide Oloyede
- & Matthew P. DeLisa
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| Open AccessImmune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial
Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.
- Youyi Fong
- , Yunda Huang
- & Peter B. Gilbert
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Article
| Open AccessEffectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5
In this study, the authors estimate the effectiveness of the mRNA-1273 (Moderna) vaccine for Omicron subvariants using data from the USA on ~31,000 cases and ~92,000 matched controls. They find that effectiveness against infection waned rapidly after third and fourth doses, but effectiveness against hospitalization remained high.
- Hung Fu Tseng
- , Bradley K. Ackerson
- & Lei Qian