vectored vaccine
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2022 ◽  
Vol 12 ◽  
Author(s):  
Liwei Li ◽  
Jinxia Chen ◽  
Zhengda Cao ◽  
Yunlei Cao ◽  
Ziqiang Guo ◽  
...  

The recombinant bivalent live vectored vaccine rPRRSV-E2 has been proved to be a favorable genetic engineering vaccine against classical swine fever (CSF) and highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS). NADC30-like strains have recently emerged in China and caused severe disease, and it is necessary to evaluate the vaccine candidate for the currently circulating viruses. This study established a good challenge model to evaluate the candidate rPRRSV-E2 vaccine in preventing infection with a representative NADC30-like strain (ZJqz21). It was shown that the challenge control piglets displayed clinical signs typical of PRRSV, including a persistent fever, dyspnea, moderate interstitial pneumonia, lymph node congestion, and viremia. In contrast, the rPRRSV-E2 vaccination significantly alleviated the clinical signs, yielded a high level of antibodies, provided adequate protection against challenge with ZJqz21, and inhibited viral shedding and the viral load in target tissues. Our results demonstrated that the recombinant bivalent live vectored vaccine strain rPRRSV-E2 can provide efficient protection against the challenge of heterologous circulating NADC30-like strain and could be a promising vaccine candidate for the swine industry.


2021 ◽  
Author(s):  
Tamarand L Darling ◽  
Boaling Ying ◽  
Bradley Whitener ◽  
Laura VanBlargan ◽  
Traci L Bricker ◽  
...  

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune evasion properties have arisen, which could jeopardize recently deployed vaccine and antibody-based countermeasures. Here, we evaluated in mice and hamsters the efficacy of preclinical non-GMP Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) South American variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Immunization of 129S2 and K18-human ACE2 transgenic mice with mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Thus, immunity induced by mRNA-1273 or Ad26.COV2.S vaccines can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models.


2021 ◽  
Author(s):  
Carina CD Joe ◽  
Rameswara R Segireddy ◽  
Cathy Oliveira ◽  
Adam Berg ◽  
Yuanyuan Li ◽  
...  

The Coalition for Epidemic Preparedness Innovations &rsquo &lsquo 100-day moonshot &rsquo aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint. We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity. Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical surge campaign with suitable prior preparation and resources, including adequate fill-and-finish capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.


2021 ◽  
Author(s):  
Bo Meng ◽  
Isabella Ferreira ◽  
Adam Abdullahi ◽  
Steven A Kemp ◽  
Niluka Goonawardane ◽  
...  

The Omicron variant emerged in southern Africa in late 2021 and is characterised by multiple spike mutations across all spike domains. Here we show that the Omicron spike confers very significant evasion of vaccine elicited neutralising antibodies that is more pronounced for ChAdOx-1 adenovirus vectored vaccine versus BNT162b2 mRNA vaccine. Indeed neutralisation of Omicron was not detectable for the majority of individuals who had received two doses of ChAdOx-1. Third dose mRNA vaccination rescues neutralisation in the short term. Despite three mutations predicted to favour spike S1/S2 cleavage, observed cleavage efficiency is lower than for wild type Wuhan-1 D614G and Delta. We demonstrate significantly lower infectivity of lung organoids and Calu-3 lung cells expressing endogenous levels of ACE2 and TMPRSS2 but similar infection as compared to Delta when using H1299 lung epithelial cells. Importantly, fusogenicity of the Omicron spike is impaired, leading to marked reduction in syncitia formation. These observations indicate that Omicron has gained immune evasion properties whilst possibly modulating properties associated with replication and pathogenicity.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1486
Author(s):  
Po-Wei Liao ◽  
Chieh-Lin Jerry Teng ◽  
Cheng-Wei Chou

We present a case of immune thrombocytopenia (ITP) induced by the chimpanzee adenovirus-vectored vaccine, without evidence of thrombosis, eight days after vaccine administration. The thrombocytopenia condition improved after administering steroid treatment. This adenovirus vaccine had been reported to induce rare side effects, such as immune thrombotic thrombocytopenia. This case report showed that it could also induce immune thrombocytopenia without the presence of thrombosis. Therefore, we should be cautious of this rare side effect as global vaccine administrations against coronavirus disease increase.


2021 ◽  
Vol 6 (12) ◽  
pp. e007321
Author(s):  
Samuel Cross ◽  
Yeanuk Rho ◽  
Henna Reddy ◽  
Toby Pepperrell ◽  
Florence Rodgers ◽  
...  

ObjectivesThe Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19, Vaxzevira or Covishield) builds on two decades of research and development (R&D) into chimpanzee adenovirus-vectored vaccine (ChAdOx) technology at the University of Oxford. This study aimed to approximate the funding for the R&D of ChAdOx and the Oxford–AstraZeneca vaccine and to assess the transparency of funding reporting mechanisms.MethodsWe conducted a scoping review and publication history analysis of the principal investigators to reconstruct R&D funding the ChAdOx technology. We matched award numbers with publicly accessible grant databases. We filed freedom of information (FOI) requests to the University of Oxford for the disclosure of all grants for ChAdOx R&D.ResultsWe identified 100 peer-reviewed articles relevant to ChAdOx technology published between January 2002 and October 2020, extracting 577 mentions of funding bodies from acknowledgements. Government funders from overseas (including the European Union) were mentioned 158 times (27.4%), the UK government 147 (25.5%) and charitable funders 138 (23.9%). Grant award numbers were identified for 215 (37.3%) mentions; amounts were publicly available for 121 (21.0%). Based on the FOIs, until December 2019, the biggest funders of ChAdOx R&D were the European Commission (34.0%), Wellcome Trust (20.4%) and Coalition for Epidemic Preparedness Innovations (17.5%). Since January 2020, the UK government contributed 95.5% of funding identified. The total identified R&D funding was £104 226 076 reported in the FOIs and £228 466 771 reconstructed from the literature search.ConclusionOur study approximates that public and charitable financing accounted for 97%–99% of identifiable funding for the ChAdOx vaccine technology research at the University of Oxford underlying the Oxford–AstraZeneca vaccine until autumn 2020. We encountered a lack of transparency in research funding reporting.


2021 ◽  
Author(s):  
Phillip Hicks ◽  
Jonna B. Westover ◽  
Tomaz B Manzoni ◽  
Brianne Roper ◽  
Gabrielle L Rock ◽  
...  

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 8,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation and promiscuity in incorporating foreign glycoproteins into its virions. In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity and efficacy in mice. We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of Ifnar-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection against lethal SFTSV challenge. Additionally, passive transfer of sera from immunized IFNAR-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects mice against challenge with the closely related Heartland virus despite low neutralizing titers to the virus. Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pawan Dulal ◽  
Robabeh Gharaei ◽  
Adam Berg ◽  
Adam A. Walters ◽  
Nicholas Hawkins ◽  
...  

The original version of this Article contained an error.


2021 ◽  
Vol 9 (11) ◽  
pp. e003480
Author(s):  
Anna Morena D'Alise ◽  
Guido Leoni ◽  
Maria De Lucia ◽  
Francesca Langone ◽  
Linda Nocchi ◽  
...  

BackgroundA number of different immune pathways are involved in the effective killing of cancer cells, collectively named as the ‘Cancer Immunity Cycle’. Anti-PD-1 checkpoint blockade (CPB) therapy is active on one of these pathways and reinvigorates anticancer T cell immunity, leading to long-term responses in a limited fraction of patients with cancer. We have previously shown that neoantigens-based adenovirus vectored vaccine in combination with anti-PD-1 further expands pre-existing anticancer immunity and elicits novel neoantigen-specific T cells thereby increasing efficacy to 50% of tumor clearance in mice. Here we added a third component to the CPB plus vaccine combination, which is able to modify the suppressive tumor microenvironment by reducing the number of tumor-infiltrating regulatory T cells (Tregs), as strategy for improving the therapeutic efficacy and overcoming resistance.MethodsThe antitumor efficacy of anti-PD-1, neoantigen vaccine and Treg modulating agents, either Bempegaldesleukin (BEMPEG: NKTR-214) or an anti-CTLA-4 mAb with Treg-depleting activity, was investigated in murine tumor models. We evaluated tumor growth in treated animals, neoantigen-specific T cells in tumors, tumor-infiltrating lymphocytes (TILs) and intratumoral Tregs.ResultsThe addition of BEMPEG or anti-CTLA-4 to the combination of vaccine and anti-PD-1 led to complete eradication of large tumors in nearby 100% of treated animals, in association with expansion and activation of cancer neoantigen-specific T cells and reduction of tumor-infiltrating Tregs.ConclusionThese data support the notion that the integrated regulation of three steps of the cancer immunity cycle, including expansion of neoantigen-specific T cells, reversal of the exhausted T cell phenotype together with the reduction of intratumoral Tregs may represent a novel rationally designed drug combination approach to achieve higher cure rates.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2127
Author(s):  
William M. de Souza ◽  
Stéfanie P. Muraro ◽  
Gabriela F. Souza ◽  
Mariene R. Amorim ◽  
Renata Sesti-Costa ◽  
...  

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8–3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.


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