Replication-deficient Sendai virus expressing human norovirus capsid protein elicits robust NoV-specific antibody and T-cell responses in mice.

Human norovirus (HuNoV) is a major global cause of acute gastroenteritis, with vaccine development facing several challenges. Despite years of research, there are currently no licensed vaccines available for controlling HuNoVs. Here, we describe the construction and testing of a replication-deficient Sendai virus (SeV) vector as a potential vaccine candidate against the HuNoV GII.

Activation of CD4 T cells during prime immunization determines the success of a therapeutic hepatitis B vaccine in HBV-carrier mouse models.

Background & Aims: We recently developed a heterologous therapeutic vaccination scheme (TherVacB) comprising a particulate protein prime followed by a modified vaccinia-virus Ankara (MVA)-vector boost for the treatment of HBV. However, the key determinants required to overcome HBV-specific immune tolerance remain unclear. Herein, we aimed to study new combination adjuvants and unravel factors that are essential for the antiviral efficacy of TherVacB.

Efficient Delivery of Human Cytomegalovirus T Cell Antigens by Attenuated Sendai Virus Vectors.

Human cytomegalovirus (HCMV) represents a major cause of clinical complications during pregnancy as well as immunosuppression, and the licensing of a protective HCMV vaccine remains an unmet global need. Here, we designed and validated novel Sendai virus (SeV) vectors delivering the T cell immunogens IE-1 and pp65. To enhance vector safety, we used a replication-deficient strain (rdSeV) that infects target cells in a nonproductive manner while retaining viral gene expression.

A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features.

Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector.

We developed a novel vaccine platform based on a paramyxoviral, genome replication-deficient Sendai virus vector that can express heterologous genes inserted into the genome. To validate the novel approach in vivo, we generated a combined vaccine candidate against human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (PIV3). The present study compares two different methods of displaying heterologous antigens: (i) the RSV fusion (F) protein, encoded as a secretable version in an additional transcription unit, serves as an antigen only after being expressed in infected cells; (ii) PIV3 fusion (F) and hemagglutinin-neuraminidase (HN) genes, replacing Sendai counterparts in the vector genome, are also expressed as structural components on the surface of vaccine particles.

Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector.

The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector.

Evaluation of nucleocapsid and phosphoprotein p functionality as critical factors during the early phase of paramyxoviral infection.

In the beginning of a paramyxovirus infection after cell entry viral survival depends on efficient primary (1°) transcription and on the stability of only one input nucleocapsid. Here we examined the influence of the viral polymerase co-factor phosphoprotein P on the very early phase of an infection, i.e.

Quantitative proteomics reveals subset-specific viral recognition in dendritic cells.

Dendritic cell (DC) populations consist of multiple subsets that are essential orchestrators of the immune system. Technological limitations have so far prevented systems-wide accurate proteome comparison of rare cell populations in vivo. Here, we used high-resolution mass spectrometry-based proteomics, combined with label-free quantitation algorithms, to determine the proteome of mouse splenic conventional and plasmacytoid DC subsets to a depth of 5,780 and 6,664 proteins, respectively.

Recombinant measles viruses expressing single or multiple antigens of human immunodeficiency virus (HIV-1) induce cellular and humoral immune responses.

Recombinant measles viruses (rMV) based on the live attenuated measles vaccine strain (MVb) expressing antigens of HIV-1 clade B were generated by reverse genetics. Recombinants expressing single or double antigens of HIV-1 (rMV-HIV) were genetically highly stable on human diploid cells. The production process of these viruses was essentially similar to the parental MV strain, yielding comparative end titers.

Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses.

Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised spike glycoprotein (S) or nucleocapsid protein (N) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were generated (rMV-S and rMV-N). Both recombinant viruses stably expressed the corresponding SARS-CoV proteins, grew to similar end titres as the parental strain and induced high antibody titres against MV and the vectored SARS-CoV antigens (S and N) in transgenic mice susceptible to measles infection. The antibodies induced by rMV-S had a high neutralising effect on SARS-CoV as well as on MV.

De novo synthesis of N and P proteins as a key step in Sendai virus gene expression.

Among the members of the paramyxovirus family, the transcription process and the components involved have been studied under in vitro conditions thus far. Here, we reexamined the function of the viral RNA-dependent RNA polymerase through infection studies with Sendai virus (SeV) N and P deletion (Delta) mutants. To elucidate solely transcription-specific processes, all virus mutants also were rendered deficient in genome replication.

Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner.

Induction of apoptosis during Sendai virus (SeV) infection has previously been documented to be triggered by initiator caspases (for strain F) or by a contribution of the cellular protein TIAR (T-cell-activated intracellular antigen-related) (for strain Z). Here, evidence was provided that both TIAR and caspases are simultaneously involved in apoptosis induction as a result of infection with SeV strain F. SeV F infection induced death in all tested cell lines, which could only be partially prevented through the pan-caspase inhibitor z-VAD-fmk.