Safety, immunogenicity and antibody persistence of a bivalent Beta-containing booster vaccine against COVID-19: a phase 2/3 trial

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2388 - 2397

Published: Oct. 6, 2022

Updated immunization strategies are needed to address multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here we report interim results from an ongoing, open-label phase 2/3 trial evaluating the safety and immunogenicity of bivalent Coronavirus Disease 2019 (COVID-19) vaccine candidate mRNA-1273.211, which contains equal mRNA amounts encoding ancestral SARS-CoV-2 Beta variant spike proteins, as 50-µg (n = 300) 100-µg 595) first booster doses administered approximately 8.7-9.7 months after mRNA-1273 primary series ( NCT04927065 ). The objectives were evaluate reactogenicity mRNA-1273.211 demonstrate non-inferior antibody responses compared series. Additionally, a pre-specified objective was superior previously authorized booster. (50-µg or 100-µg) 28 days elicited higher neutralizing against than those second mRNA‑1273 dose NCT04470427 Antibody 180 also NCT04405076 ) Beta, Omicron BA.1 Delta variants, all met. profile (50-µg) similar (50-µg). Immunization with does not set ceiling response, elicits robust response titers that likely be protective COVID-19. These indicate vaccines can induce potent, durable broad providing new tool in emerging

Language: Английский

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Antibody-mediated neutralization of SARS-CoV-2

Immunity, Journal Year: 2022, Volume and Issue: 55(6), P. 925 - 944

Published: May 13, 2022

Language: Английский

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mRNA vaccines in disease prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance recent years against worldwide plague COVID-19. The huge superiority regarding efficacy, safety, large-scale manufacture encourages pharmaceutical industries biotechnology companies expand application a diverse array despite nonnegligible problems design, fabrication, mode administration. This review delves into technical underpinnings vaccines, covering synthesis, delivery, adjuvant technologies. Moreover, this presents systematic retrospective analysis logical well-organized manner, shedding light on representative employed various diseases. scope extends across infectious cancers, immunological tissue damages, rare showcasing versatility potential therapeutic areas. Furthermore, engages prospective discussion current challenge direction for advancement utilization vaccines. Overall, comprehensive serves valuable resource researchers, clinicians, industry professionals, providing understanding aspects, historical context, future prospects fight

Language: Английский

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SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

MedComm, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

Abstract New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread the virus in ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), latest variant concern (VOC), has so far shown exceptional and infectivity established itself as dominant recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for recognition binding to host cell angiotensin‐converting enzyme receptors. harbors cluster substitutions/deletions/insertions, more than 30 mutations are located spike. Some noticeable mutations, including K417N, T478K, N501Y, P681H, shared with previous VOCs Alpha, Beta, Gamma, or Delta have been proven be associated higher transmissibility, viral infectivity, immune evasion potential. Studies revealed that partially resistant neutralizing activity therapeutic antibodies convalescent sera, which poses significant challenges clinical effectiveness current vaccines antibodies. We provide comprehensive analysis summary epidemiology escape mechanisms variant. also suggest some strategies against This review, therefore, aims information further research efforts prevent contain impact new during

Language: Английский

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SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(6), P. 880 - 886.e4

Published: March 25, 2022

The SARS-CoV-2 Omicron variant escapes neutralizing antibodies elicited by vaccines or infection. However, whether triggers cross-reactive humoral responses to other variants of concern (VOCs) remains unknown. We used plasma from 20 unvaccinated and 7 vaccinated individuals infected BA.1 test binding, Fc effector function, neutralization against VOCs. In individuals, function binding targeted VOCs at comparable levels. BA.1-triggered was not extensively for (14- 31-fold titer reduction), we observed 4-fold decreased titers BA.2. contrast, vaccination followed breakthrough infection associated with improved cross-neutralization exceeding 1:2,100. This has important implications the vulnerability Omicron-infected reinfection circulating emerging Although Omicron-based immunogens might be adequate boosters, they are unlikely superior existing priming in SARS-CoV-2-naive individuals.

Language: Английский

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Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary responses

Immunity, Journal Year: 2022, Volume and Issue: 55(10), P. 1856 - 1871.e6

Published: Aug. 4, 2022

Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing recruitment GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that elicited during primary humoral responses shaped naive cell exposures. The from could either enhance or, conversely, restrict GC participation of cells: broad-binding, low-affinity, low-titer enhanced recruitment, whereas, contrast, high titers high-affinity, mono-epitope-specific attenuated cognate recruitment. Thus, directionality intensity effect was determined antibody concentration, affinity, epitope specificity. Circulating can, therefore, be important determinants antigen immunogenicity. Future vaccines may need overcome-or could, alternatively, leverage-the effects circulating subsequent

Language: Английский

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Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(662)

Published: Sept. 14, 2022

Emergence of SARS-CoV-2 variants concern (VOCs), including the highly transmissible Omicron and Delta strains, has posed constant challenges to current COVID-19 vaccines that principally target viral spike protein (S). Here, we report a nucleoside-modified messenger RNA (mRNA) vaccine expresses more conserved nucleoprotein (mRNA-N) show mRNA-N vaccination alone can induce modest control SARS-CoV-2. Critically, combining with clinically proven S-expressing mRNA (mRNA-S+N) induced robust protection against both variants. In hamster models VOC challenge, demonstrated that, compared mRNA-S alone, combination mRNA-S+N not only in lungs but also provided enhanced upper respiratory tract. vivo CD8

Language: Английский

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Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques

Nature, Journal Year: 2023, Volume and Issue: 626(7998), P. 385 - 391

Published: Dec. 14, 2023

Abstract A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with Omicron subvariants 1,2 , although still severe disease. Enhanced mucosal immunity may be required to block and onward transmission. Intranasal administration has proven inconsistent 3–7 suggesting alternative immunization strategies required. Here we show intratracheal boosting a bivalent Ad26-based vaccine results in substantial induction humoral cellular near-complete BQ.1.1 challenge. total 40 previously immunized rhesus macaques were boosted Ad26 by the intramuscular, intranasal routes, or mRNA route. route led expansion neutralizing antibodies, IgG IgA binding CD8 + CD4 T cell responses, which exceeded those induced intramuscular routes. Intratracheal also robust upregulation cytokine, natural killer, B pathways lungs. After challenge high dose BQ.1.1, provided protection, whereas other proved less effective. Protective efficacy correlated best immune responses. These data demonstrate these induce immunity, feasibility developing respiratory viral infections.

Language: Английский

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Factors, enablers and challenges for COVID-19 vaccine development

BMJ Global Health, Journal Year: 2023, Volume and Issue: 8(6), P. e011879 - e011879

Published: June 1, 2023

The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators industry overcome traditional challenges for the development vaccine candidates reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical regulatory reviews were among key factors contributed accelerating approval vaccines. rapid vaccines benefited previous scientific innovations such as mRNA recombinant vectors proteins. This has created new era vaccinology, with powerful platform technologies model development. These lessons learnt highlight need strong leadership, bring together global health organisations, manufacturers, scientists, private sector, civil society philanthropy, generate innovative, fair equitable access mechanisms populations worldwide build more efficient effective ecosystem prepare other pandemics may emerge. With longer-term view, must be developed incentives expertise manufacturing can leveraged low/middle-income countries markets ensure equity in innovation, delivery. creation hubs appropriate sustained training, particular Africa, is certainly way future public safeguard economic security continent guarantee access, however capacity interpandemic period.

Language: Английский

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Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines

Nature, Journal Year: 2024, Volume and Issue: 630(8018), P. 950 - 960

Published: May 15, 2024

Language: Английский

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