A5073701561- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Virology and Viral Diseases
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Parvovirus B19 Infection Studies
- Pneumonia and Respiratory Infections
- Viral Infections and Vectors
- Viral Infections and Immunology Research
- interferon and immune responses
- Mosquito-borne diseases and control
- Vector-Borne Animal Diseases
- Plant Virus Research Studies
- Autism Spectrum Disorder Research
- Long-Term Effects of COVID-19
- Bacterial Infections and Vaccines
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
National Institute of Allergy and Infectious Diseases
2011-2024
National Institutes of Health
2010-2024
Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail
2005-2012
Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory-tract disease worldwide. A vaccine or generally effective antiviral drug not yet available. We designed new live attenuated RSV candidates by codon-pair deoptimization (CPD). Specifically, ORFs were recoded rearranging existing synonymous codons to increase content underrepresented codon pairs. Amino acid coding was completely unchanged. Four CPD genomes in which indicated recoded: Min...
We recently demonstrated that the respiratory syncytial virus (RSV) NS1 protein, an antagonist of host type I interferon (IFN-I) production and signaling, has a suppressive effect on maturation human dendritic cells (DC) was only partly dependent released IFN-I. Here we investigated whether affects ability DC to activate CD8+ CD4+ T cells. Human were infected with RSV deletion mutants lacking and/or NS2 genes assayed for autologous in vitro, which analyzed by multi-color flow cytometry....
Infectious bursal disease virus (IBDV) causes an economically significant of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, the relative contributions two genome segments, A B, to this phenomenon are known. Isolate 94432 has been shown previously be genetically related vvIBDVs but exhibits atypical antigenicity does cause Here full-length was determined, a reverse genetics...
Significance Pediatric SARS-CoV-2 infections, though generally mild, are associated with substantial morbidity and contribute to transmission dynamics. No vaccines available for young children. Bovine/human parainfluenza virus 3 (B/HPIV3) vectors intranasal immunization of children were evaluated previously in phase 1/2 studies well-tolerated as 2 mo age. This manuscript describes a B/HPIV3 vector expressing prefusion-stabilized version the S protein (S-2P), shows that single dose is highly...
The purpose of this study was to compare the molecular epidemiology infectious bursal disease virus (IBDV) segments A and B 50 natural or vaccine IBDV strains that were isolated produced between 1972 2002 in 17 countries from four continents, with phenotypes ranging attenuated very virulent (vv). These subjected sequence phylogenetic analysis based on partial sequences genome B. Although there is co-evolution two (70 % kept same genetic relatives segment A- B-defined consensus trees),...
ABSTRACT Human respiratory syncytial virus (RSV) is the most important agent of serious pediatric tract disease worldwide. One main characteristics RSV that it readily reinfects and causes throughout life without need for significant antigenic change. The encodes nonstructural protein 1 (NS1) NS2, which are known to suppress type I interferon (IFN) production signaling. In present study, we monitored maturation human monocyte-derived myeloid dendritic cells (DC) following inoculation with...
Human respiratory syncytial virus (RSV) is an enveloped RNA that the most important viral cause of acute pediatric lower tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement host factors in RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as factor involved infection. ARP2 knockdown did not reduce entry, markedly gene expression during first 24 hr...
Background Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has bi-segmented double-stranded RNA genome. Segments A and B encode capsid, ribonucleoprotein non-structural proteins, or polymerase (RdRp), respectively. Since late eighties, very virulent (vv) strains have emerged in Europe inducing up 60% mortality. Although some progress been made understanding molecular biology IBDV, basis for pathogenicity vvIBDV still not fully...
Significance Recoding viral genomes by numerous synonymous substitutions provided live attenuated vaccine candidates predicted to have a low risk of reversion. However, their stability under selective pressure was largely unknown. We evaluated the phenotypic reversion representative genome-scale deoptimized human respiratory syncytial virus (RSV) in context strong pressure. found that bearing L-polymerase ORF evolved escape temperature sensitivity restriction mutations L and multiple other...
The continuous emergence of new SARS-CoV-2 variants requires that COVID vaccines be updated to match circulating strains. We generated B/HPIV3-vectored expressing 6P-stabilized S protein the ancestral, B.1.617.2/Delta, or B.1.1.529/Omicron as pediatric for intranasal immunization against HPIV3 and characterized these in hamsters. Following immunization, B/HPIV3 vectors replicated upper lower respiratory tract induced mucosal serum anti-S IgA IgG. ancestral B.1.617.2/Delta-derived S-6P...
Human respiratory syncytial virus (HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and parainfluenza type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A (IAV) largely depends on more complete Antigen presentation dendritic cells (DC) is critical in initiating the adaptive immune response. uptake DC induces maturational changes that include...
Abstract Immunization via the respiratory route is predicted to increase effectiveness of a SARS-CoV-2 vaccine. Here, we evaluate immunogenicity and protective efficacy one or two doses live-attenuated murine pneumonia virus vector expressing prefusion-stabilized spike protein (MPV/S-2P), delivered intranasally/intratracheally male rhesus macaques. A single dose MPV/S-2P highly immunogenic, second increases magnitude breadth mucosal systemic anti-S antibody responses levels dimeric IgA in...
Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there no approved vaccine. Here, we describe development live-attenuated RSV vaccine candidate Min AL as well engineered derivatives. was attenuated by codon-pair deoptimization (CPD) seven 11 open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). replicated efficiently vitro at permissive temperature 32°C highly...
Background Human respiratory syncytial virus (HRSV), and to a lesser extent human metapneumovirus (HMPV) parainfluenza type 3 (HPIV3), re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought be viral interference with dendritic cell (DC)-mediated stimulation CD4+ T cells. Methodology, Principal Findings We infected monocyte-derived DC purified HRSV, HMPV, HPIV3, or influenza A (IAV) compared their ability induce...
Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to incomplete short-lived. We used gene-deletion viruses evaluate role attachment G small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC) vitro subsequent MDDC maturation activation autologous T cells. with deletion (ΔSHG) exhibited increased...
Live-attenuated pediatric vaccines for intranasal administration are being developed human respiratory syncytial virus (RSV), an important worldwide pathogen that lacks a licensed vaccine or suitable antiviral drug. We evaluated prime-boost strategy in which primary immunization with RSV was boosted by secondary chimeric recombinant bovine/human parainfluenza type 3 (rB/HPIV3) vector expressing the fusion F protein. The vector-expressed protein had been engineered (DS-Cav1 mutations)...
Current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are administered parenterally and appear to be more protective in the lower versus upper tract. Vaccines needed that directly stimulate immunity tract, as well systemic immunity. We used avian paramyxovirus type 3 (APMV3) an intranasal vaccine vector express SARS-CoV-2 spike (S) protein. A lack of pre-existing humans attenuation by host-range restriction make APMV3 a interest. The S protein was stabilized...
ABSTRACT The pro- and anti-inflammatory pathways that determine the balance of inflammation viral control during SARS-CoV-2 infection are not well understood. Here we examine roles IFNγ IL-10 in regulating inflammation, immune cell responses replication rhesus macaques. blockade tended to decrease lung based on 18 FDG-PET/CT imaging but had no major impact innate lymphocytes, neutralizing antibodies, or antigen-specific T cells. In contrast, transiently increased enhanced accumulation...
We subjected various open reading frames (ORFs) in the genome of respiratory syncytial virus (RSV) to codon pair optimization (CPO) by increasing content pairs that are overrepresented human without changing overall usage and amino acid sequences. CPO has potential increase expression encoded protein(s). Four viruses were made: Max A (with NS1, NS2, N, P, M, SH ORFs), B G F), L L), FLC all ORFs except M2-1 M2-2). Because possibility increased viral replication, each was attenuated inclusion...
The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera...
Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin–neuraminidase (HN), and polymerase (L) were modified singly in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP,...