Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron.

BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTSThe 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSIONThese results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

Genetic Characteristics and Pathogenicity of a Novel Porcine Deltacoronavirus Southeast Asia-Like Strain Found in China.

Farmers involved in the lucrative pork trading business between China and Southeast Asian countries should be aware of a recently discovered novel porcine deltacoronavirus (PDCoV) in Guangxi province, China. A PDCoV strain, CHN/GX/1468B/2017, was isolated from the small intestinal contents of piglets with diarrhea from this region, with a titer of 1 × 108.0 TCID50/mL on LLC-PK cells. The full-length genome sequence consists of 25,399 nt as determined by next-generation sequencing and this was deposited in the GenBank (accession number MN025260.1). Genomic analysis showed that CHN/GX/1468B/2017 strain had 96.9~99.4% nucleotide homology with other 87 referenced PDCoV strains from different areas, and contained 6 and 9-nt deletions at positions 1,733~1,738 and 2,804~2,812, respectively, in the ORF1a gene. Phylogenetic analyses based on the whole gene sequence as well as S protein and ORF1a/1b protein sequences all showed that this strain was closely related to the Southeast Asia strain. When 7-day-old piglets were inoculated orally with the CHN/GX/1468B/2017 strain, they developed severe diarrhea, with a peak of fecal viral shedding at 4 days post-infection. Although no death or fever were observed, the CHN/GX/1468B/2017 strain produced a wide range of tissue tropism, with the main target being the intestine. Importantly, the VH:CD ratios of the jejunum and ileum in infected piglets were significantly lower than controls. These results indicate that CHN/GX/1468B/2017, isolated in China, is a novel PDCoV Southeast Asia-like strain with distinct genetic characteristics and pathogenicity. This finding enriches the international information on the genetic diversity of PDCoV.

Complete Genome Sequencing, Molecular Epidemiological, and Pathogenicity Analysis of Pigeon Paramyxoviruses Type 1 Isolated in Guangxi, China during 2012-2018.

Newcastle disease is an important poultry disease that also affects Columbiform birds. The viruses adapted to pigeons and doves are referred to as pigeon paramyxoviruses 1 (PPMV-1). PPMV-1 are frequently isolated from pigeons worldwide and have the potential to cause disease in chickens. The complete genomes of 18 PPMV-1 isolated in China during 2012-2018 were sequenced by next-generation sequencing (NGS). Comprehensive phylogenetic analyses showed that five of the viruses belong to sub-genotype VI1.2.1.1.2.1 and 13 isolates belong to sub-genotype VI.2.1.1.2.2. The results demonstrate that these sub-genotypes have been predominant in China during the last decade. The viruses of these sub-genotypes have been independently maintained and continuously evolved for over 20 years, and differ significantly from those causing outbreaks worldwide during the 1980s to 2010s. The viral reservoir remains unknown and possibilities of the viruses being maintained in both pigeon farms and wild bird populations are viable. In vivo characterization of the isolates' pathogenicity estimated mean death times between 62 and 114 hours and intracerebral pathogenicity indices between 0.00 and 0.63. Cross-reactivity testing showed minor antigenic differences between the studied viruses and the genotype II LaSota vaccine. These data will facilitate PPMV-1 epidemiology studies, vaccine development, and control of Newcastle disease in pigeons and poultry.

Complete Genome Sequence of a Novel Porcine Circovirus Type 3 Strain, CH/GX/1776D/2017, Isolated from Guangxi, China.

Porcine circovirus type 3 (PCV3) was first described in 2016 in U.S. swine herds as a pathogenic agent for pigs. To date, PCV3 has been reported to be widely circulating in the United States, China, South Korea, Brazil, Italy, and Poland. Here, we report the genome sequence of a PCV3 strain (CH/GX/1776D/2017) isolated from Guangxi Province in southern China. The sequence data presented in this study will help us better understand the molecular characteristics and genetic diversity of PCV3 in China.

Full-Length Genome Sequence of Japanese Encephalitis Virus Strain FC792, Isolated from Guangxi, China.

We report here the complete genomic sequence of Japanese encephalitis virus (JEV) strain FC792, isolated from aborted fetuses of sows which were unimmunized with JEV vaccines in Guangxi Province, southern China. The complete JEV genome of strain FC792 had the highest nucleotide homology (99.7%) and amino acid identity (99.4%) with the sequence of JEV strain SA14-14-2 (GenBank accession number AF315119). Phylogenetic analysis showed that strain FC792 had the closest phylogenetic relationship to the sequence of strain YUNNAN0901 (GenBank accession number JQ086762). This study will help us understand the molecular pathogenesis and genetic diversity of genotype III Japanese encephalitis virus in pigs.

Full-Length Genome Sequence of Porcine Epidemic Diarrhea Virus Strain CH/GX/2015/750A.

We report here the complete genome sequence of porcine epidemic diarrhea virus (PEDV) strain CH/GX/2015/750A (750A), which was isolated from a suckling piglet with watery diarrhea in Guangxi, China. The isolate is genetically close to other recent Chinese variant PEDVs and distinct from the classical PEDVs.

Complete genome sequence of porcine parvovirus N strain isolated from guangxi, china.

We report here the complete genomic sequence of the porcine parvovirus (PPV) N strain, isolated in 1989 from the viscera of a stillborn fetus farrowed by a gilt in Guangxi, southern China. Phylogenetic analyses suggest that the PPV-N strain is closely related to attenuated PPV NADL-2 strains. The PPV-N strain has good immunogenicity, genetic stability, and safety.