Full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice conferred by MVA-CoV2-S vaccine candidate

Nature Neuroscience, Год журнала: 2023, Номер 26(2), С. 226 - 238

Опубликована: Янв. 9, 2023

Язык: Английский

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Exosome-Based Multivalent Vaccine: Achieving Potent Immunization, Broadened Reactivity, and Strong T-Cell Responses with Nanograms of Proteins

Microbiology Spectrum, Год журнала: 2023, Номер 11(3)

Опубликована: Апрель 24, 2023

Currently approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first were developed rapidly using mRNA delivered by lipid nanoparticles but required ultralow-temperature storage and had limited immunity variations in spike. Subsequently, protein-based developed, which offer broader require significant time for development use of an adjuvant boost immune response. Here, exosomes used deliver a bivalent vaccine two independent viral proteins used. Exosomes engineered express either SARS-CoV-2 delta (Stealth X-Spike [STX-S]) or more conserved nucleocapsid X-Nucleocapsid [STX-N]) surface. When administered as single product (STX-S STX-N) combination (STX-S+N), both STX-S STX-N induced strong immunization with production potent humoral cellular responses. Interestingly, these results obtained administration only nanograms without adjuvant. In animal models (mouse rabbit), STX-S+N resulted increased antibody production, neutralizing antibodies cross-reactivity other variants spike, T-cell Importantly, no competition responses was observed, allowing delivery improved These data show that StealthX exosome platform has enormous potential revolutionize vaccinology combining advantages recombinant into superior, generated, low-dose resulting potent, IMPORTANCE pandemic emergency brought light need new generation induce longer-lasting, While played critical role during reducing hospitalization rates deaths, efficient approaches are needed. A multivalent, could meet this urgent due high speed development, manufacturability, ability produce response, response able broadly combat infection minimum number injections.

Язык: Английский

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OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 19, 2023

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) genetically fused to oligoDOM ® , self-assembling domain which improves antigen immunogenicity. including N as an antigenic target proposed new vaccine candidate providing broad-spectrum protection sarbecoviruses. demonstrated its ability trigger cross-reactive T cell responses and cross-protection three (B.1 Europe, Delta B.1.617.2, Omicron B.1.1.529) in hamster challenge model, evidenced by lower weight loss, lung viral loads, reduced histopathological lesions.

Язык: Английский

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An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants

Pathogens, Год журнала: 2025, Номер 14(1), С. 23 - 23

Опубликована: Янв. 1, 2025

The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. been responsible for millions deaths worldwide since its first identification in late 2019. Several actions have taken prevent the disease, including unprecedented fast development and vaccination campaigns, which were pivotal reducing symptoms deaths. Given impact pandemic, continuous changes virus, present vaccine technologies, this review analyzes how, so far, we met challenge by emergence new variants discusses how next-generation pan-coronavirus vaccines, enhanced longevity breadth immune responses, may be tackled alternative administration routes antigen delivery platforms. By addressing these critical aspects, aims contribute ongoing efforts achieve long-term control COVID-19, stimulating discussion work on vaccines capable facing future waves infection.

Язык: Английский

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LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 4, 2025

Lipid nanoparticle (LNP)-mRNA vaccines have demonstrated protective capability in combating SARS-CoV-2. Their extensive deployment across the global population leads to broad presence of T-cell immunity against SARS-CoV-2 spike protein, presenting an opportunity harness this immunological response as a universal antigen target for cancer treatment. Herein, we design and synthesize series amino alcohol- or acid-derived ionizable lipids (AA lipids) develop LNP-RNA-based presentation platform redirect spike-specific mouse models. First, prime-boost regimen, AA2 LNP encapsulating mRNA elicit stronger epitopes compared FDA-approved LNPs (ALC-0315 SM-102), highlighting superior delivery efficiency LNP. Next, AA15V efficiently delivers self-amplifying RNAs (saRNAs) encoding epitope-loaded single-chain trimer (sSE-SCT) MHC I molecules into tumor tissues, thereby inducing epitopes. Our results show that single intratumoral (i.t.) treatment LNP-sSE-SCTs suppresses growth extends survival B16F10 melanoma A20 lymphoma tumor-bearing mice vaccinated with LNP-spike mRNA. Additionally, enable SE-SCT expression ex vivo human glioblastoma lung samples, suggesting its potential clinical translation.

Язык: Английский

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Cross-protective immunity following coronavirus vaccination and coronavirus infection

Journal of Clinical Investigation, Год журнала: 2021, Номер 131(24)

Опубликована: Окт. 8, 2021

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if can also protect other coronaviruses that may infect humans in the future. Here, we show elicited cross-protective immune responses heterologous coronaviruses. In particular, a 1 (SARS-CoV-1) vaccine developed 2004 and known to SARS-CoV-1 conferred robust protection SARS-CoV-2 mice. Similarly, prior infections distinct Cross-reactive immunity was reported patients with disease 2019 (COVID-19) individuals who received vaccines, transfer of plasma from these into mice improved challenges. These findings provide first demonstration our knowledge (and infections) confer broad establish rationale for universal vaccines.

Язык: Английский

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A modified vaccinia Ankara vaccine expressing spike and nucleocapsid protects rhesus macaques against SARS-CoV-2 Delta infection

Science Immunology, Год журнала: 2022, Номер 7(72)

Опубликована: Март 31, 2022

SARS-CoV-2 vaccines should induce broadly cross-reactive humoral and T cell responses to protect against emerging variants of concern (VOCs). Here, we inactivated the furin cleavage site (FCS) spike expressed by a modified vaccinia Ankara (MVA) virus vaccine (MVA/SdFCS) found that FCS inactivation markedly increased binding human ACE2. After vaccination mice, MVA/SdFCS induced eightfold higher neutralizing antibodies compared with MVA/S, which without inactivation, protected Beta variant. We next added nucleocapsid (MVA/SdFCS-N) tested its immunogenicity efficacy via intramuscular (IM), buccal (BU), or sublingual (SL) routes in rhesus macaques. IM spike-specific IgG serum mucosae (nose, throat, lung, rectum) neutralized homologous (WA-1/2020) heterologous VOCs, including Delta, minimal loss (<2-fold) activity. also both spike- nucleocapsid-specific CD4 CD8 blood. In contrast, SL BU vaccinations less secretions lower levels polyfunctional vaccination. challenge Delta variant, route robust protection, moderate no protection. Vaccine-induced non-neutralizing antibody effector functions positively correlated but only early Thus, MVA/SdFCS-N elicited responses, protecting VOC more effectively than other

Язык: Английский

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Cross-reactive immunity against SARS-CoV-2 N protein in Central and West Africa precedes the COVID-19 pandemic

Scientific Reports, Год журнала: 2022, Номер 12(1)

Опубликована: Июль 28, 2022

Abstract Early predictions forecasted large numbers of severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases and associated deaths in Africa. To date, Africa has been relatively spared. Various hypotheses were postulated to explain the lower than anticipated impact on public health However, contribution pre-existing immunity is yet be investigated. In this study, presence antibodies against SARS-CoV-2 spike (S) nucleocapsid (N) proteins pre-pandemic samples from Africa, Europe, South North America was examined by ELISA. The protective efficacy N specific isolated Central African donors tested vitro neutralization a mouse model infection. Antibodies S rare all populations except Gabon Senegal where prevalent. these failed neutralize virus either or vivo. Overall, study indicates that cross-reactive protein present prior pandemic. humoral does not viral fitness rodents suggesting other human immune defense mechanisms could involved. seroprevalence studies using are over-estimating circulation.

Язык: Английский

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The role of SARS-CoV-2 nucleocapsid protein in antiviral immunity and vaccine development

Emerging Microbes & Infections, Год журнала: 2022, Номер 12(1)

Опубликована: Дек. 30, 2022

ABSTRACTThe coronavirus disease 2019 (COVID-19) has caused enormous health risks and global economic disruption. This is by the severe acute respiratory syndrome 2 (SARS-CoV-2). The SARS-CoV-2 nucleocapsid protein a structural involved in viral replication assembly. There accumulating evidence indicating that multi-functional, playing key role pathogenesis of COVID-19 antiviral immunity against SARS-CoV-2. Here, we summarize its potential application prevention COVID-19, which based on inflammation, cell death, innate immunity, adaptive immunity.

Язык: Английский

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Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 29, 2023

Introduction Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although Neuro-PASC are widely documented, it is still unclear whether PASC impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to Nucleocapsid protein identify activation signatures distinguishing patients healthy convalescents. Results We report that exhibit distinct immunological composed elevated CD4 + diminished CD8 memory toward the C-terminal region when both functionally using TCR sequencing. production IL-6 correlated increased plasma levels as well heightened severity symptoms, including pain. Elevated immunoregulatory reduced pro-inflammatory antiviral response were evident in compared convalescent controls without lasting correlating worse neurocognitive dysfunction. Discussion conclude these data provide new insight into cellular immunity on pathogenesis pave way for rational design predictive biomarkers therapeutic interventions.

Язык: Английский

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