A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2.

Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N).

Patient-derived head and neck tumor slice cultures: a versatile tool to study oncolytic virus action.

Head and neck cancer etiology and architecture is quite diverse and complex, impeding the prediction whether a patient could respond to a particular cancer immunotherapy or combination treatment. A concomitantly arising caveat is obviously the translation from pre-clinical, cell based in vitro systems as well as syngeneic murine tumor models towards the heterogeneous architecture of the human tumor ecosystems. To bridge this gap, we have established and employed a patient-derived HNSCC (head and neck squamous cell carcinoma) slice culturing system to assess immunomodulatory effects as well as permissivity and oncolytic virus (OV) action.

A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity.

Functional tumor-specific cytotoxic T cells elicited by therapeutic cancer vaccination in combination with oncolytic viruses offer opportunities to address resistance to checkpoint blockade therapy. Two cancer vaccines, the self-adjuvanting protein vaccine KISIMA, and the recombinant oncolytic vesicular stomatitis virus pseudotyped with LCMV-GP expressing tumor-associated antigens, termed VSV-GP-TAA, both show promise as a single agent. Here we find that, when given in a heterologous prime-boost regimen with an optimized schedule and route of administration, combining KISIMA and VSV-GP-TAA vaccinations induces better cancer immunity than individually.

Delivery of self-amplifying RNA vaccines in in vitro reconstituted virus-like particles.

Many mRNA-based vaccines have been investigated for their specific potential to activate dendritic cells (DCs), the highly-specialized antigen-presenting cells of the immune system that play a key role in inducing effective CD4+ and CD8+ T-cell responses. In this paper we report a new vaccine/gene delivery platform that demonstrates the benefits of using a self-amplifying ("replicon") mRNA that is protected in a viral-protein capsid. Purified capsid protein from the plant virus Cowpea Chlorotic Mottle Virus (CCMV) is used to in vitro assemble monodisperse virus-like particles (VLPs) containing reporter proteins (e.

Introduction to RNA Vaccines.

RNA vaccines are attractive, because they exhibit characteristics of subunit vaccines and live-attenuated vectors, including flexible production and induction of both humoral and cellular immunity. While human proof-of-concept for RNA vaccines is still pending, the nascent field of RNA therapeutics has already attracted substantial industry and government funding as well as record investments of private venture capital. Most recently, the WHO acknowledged messenger RNA (mRNA) as a new therapeutic class.

Reduction of PMWS-associated clinical signs and co-infections by vaccination against PCV2.

The effects of a single-dose recombinant Porcine circovirus type 2 (PCV2) open reading frame 2 (ORF2) subunit vaccine were studied in a post-weaning multisystemic wasting syndrome (PMWS)-affected pig herd. A total of 1519 3-week-old piglets were allocated randomly into two treatment groups and either vaccinated against PCV2 or treated with a placebo. Study animals were followed from the time of vaccination until the end of finishing.

The effect of vaccination against porcine circovirus type 2 in pigs suffering from porcine respiratory disease complex.

A field study was conducted to investigate the effect of vaccination against porcine circovirus type 2 (PCV2) in pigs suffering from porcine respiratory disease complex (PRDC). A total of 1542 pigs were allocated randomly into two treatment groups at approximately 20 days of age. Groups received either a Baculovirus-expressed recombinant PCV2 Open Reading Frame (ORF) 2 vaccine or placebo by single intramuscular injection.

Bovine viral diarrhea virus: prevention of persistent fetal infection by a combination of two mutations affecting Erns RNase and Npro protease.

Different genetically engineered mutants of bovine viral diarrhea virus (BVDV) were analyzed for the ability to establish infection in the fetuses of pregnant heifers. The virus mutants exhibited either a deletion of the overwhelming part of the genomic region coding for the N-terminal protease N(pro), a deletion of codon 349, which abrogates the RNase activity of the structural glycoprotein E(rns), or a combination of both mutations. Two months after infection of pregnant cattle with wild-type virus or either of the single mutants, the majority of the fetuses contained virus or were aborted or found dead in the uterus.

A glycoprotein M-deleted equid herpesvirus 4 is severely impaired in virus egress and cell-to-cell spread.

To analyse the function of the equid herpesvirus 4 (EHV-4) glycoprotein M homologue (gM), two different mutated viruses (E4DeltagM-GFP and E4DeltagM-w) were generated. Both gM-negative EHV-4-mutants were characterized on complementing and on non-complementing cells and compared with E4RgM, a virus where gM-expression had been repaired. It was demonstrated in virus growth kinetics that deleting gM had a more dramatic influence on EHV-4 replication than expected.

The live attenuated bovine viral diarrhea virus components of a multi-valent vaccine confer protection against fetal infection.

Fetal infection with bovine virus diarrhea virus (BVDV) causes severe economic loss and virus spread in cattle. This study investigated the ability of modified live BVDV I and II components of a commercially available modified live virus (MLV) vaccine (Breed-Back FP 10, Boehringer Ingelheim Vetmedica Inc.) to prevent fetal infection and abortion, and therefore the birth of persistently infected animals.

Recovery of virulent and RNase-negative attenuated type 2 bovine viral diarrhea viruses from infectious cDNA clones.

Cloned cDNA derived from the genome of the virulent type 2 bovine viral diarrhea virus (BVDV) strain NY'93/C was sequenced and served for establishment of the infectious cDNA clone pKANE40A. Virus recovered from pKANE40A exhibited growth characteristics similar to those of wild-type BVDV NY'93/C and proved to be clinically indistinguishable from the wild-type virus in animal experiments. A virus mutant in which the RNase residing in the viral glycoprotein E(rns) was inactivated, revealed an attenuated phenotype.