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Polio cases can be missed by acute flaccid paralysis (AFP) case surveillance alone, emphasizing the importance of environmental surveillance (ES). In this study, to investigate the serotype distribution and epidemiological trends of poliovirus (PV), we characterized PV isolated from domestic sewage in Guangzhou City, Guangdong Province, China from 2009 to 2021. A total of 624 sewage samples were collected from the Liede Sewage Treatment Plant, and the positive rates of PV and non‐polio enteroviruses were 66.67% (416/624) and 78.37% (489/624), respectively. After sewage sample treatment, each sewage sample was inoculated in six replicate tubes of three cell lines, and 3370 viruses were isolated during the 13‐year surveillance period. Among these, 1086 isolates were identified as PV, including type 1 PV (21.36%), type 2 PV (29.19%), and type 3 PV (49.48%). Based on VP1 sequences, 1057 strains were identified as Sabin‐like, 21 strains were high‐mutant vaccines, and eight strains were vaccine‐derived poliovirus (VDPV). The numbers and serotypes of PV isolates in sewage were influenced by the vaccine switch strategy. After type 2 OPV was removed from the trivalent oral PV (OPV) vaccine and a bivalent OPV (bOPV) was adopted in May 2016, the last type 2 PV strain was isolated from sewage, with no detection thereafter. Type 3 PV isolates increased significantly and became the dominant serotype. Before and after the second vaccine switch in January 2020, that is, from the first dose of IPV and second–fourth doses of bOPV to the first two doses of IPV and third–fourth doses of bOPV, there was also a statistical difference in PV positivity rates in sewage samples. Seven type 2 VDPVs and one type 3 VDPV were identified in sewage samples in 2009–2021, and phylogenetic analysis indicated that all VDPVs isolated from ES in Guangdong are newly discovered VDPVs, different from VDPV previously discovered in China, and were classified as ambiguous VDPV. It is noteworthy that no VDPV cases were reported in AFP case surveillance in the same period. In conclusion, continued PV ES in Guangzhou since April 2008 has been a useful supplement to AFP case surveillance, providing an important basis for evaluating the effectiveness of vaccine immunization strategies. ES improves early detection, prevention, and control; accordingly, this strategy can curb the circulation of VDPVs and provide a strong laboratory basis for maintaining a polio‐free status. [ABSTRACT FROM AUTHOR]

The coronavirus disease-19 (COVID-19) pandemic has been ongoing since December 2019, with more than 6.3 million deaths reported globally as of August 2022. Despite the success of several SARS-CoV-2 vaccines, the rise in variants, some of which are resistant to the effects of vaccination, highlights the need for a so-called pan-coronavirus (universal) vaccine. Here, we performed an immunogenicity comparison of prototype vaccines containing spike protein receptor-binding domain (RBD) residues 319–541, or spike protein regions S1, S2 and S fused to a histidine-tagged or human IgG1 Fc (hFC) fragment with either a longer (six residues) or shorter (three residues) linker. While all recombinant protein vaccines developed were effective in eliciting humoral immunity, the RBD-hFc vaccine was able to generate a potent neutralizing antibody response as well as a cellular immune response. We then compared the effects of recombinant protein length and linker size on immunogenicity in vivo. We found that a longer recombinant RBD protein (residues 319–583; RBD-Plus-hFc) containing a small alanine linker (AAA) was able to trigger long-lasting, high-titer neutralizing antibodies in mice. Finally, we evaluated cross-neutralization of wild-type and mutant RBD-Plus-hFc vaccines against wild-type, Alpha, Beta, Delta and Omicron SARS-CoV-2 variants. Significantly, at the same antigen dose, wild-type RBD-Plus-hFc immune sera induced broadly neutralizing antibodies against wild-type, Alpha, Beta, Delta and Omicron variants. Taken together, our findings provide valuable information for the continued development of recombinant protein-based SARS-CoV-2 vaccines and a basic foundation for booster vaccinations to avoid reinfection with SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS‐CoV‐2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock‐in strains, and viral vector‐mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS‐CoV‐2 are unknown. Here, we perform systematic comparisons of the mouse models including K18‐hACE2 mice, KI‐hACE2 mice, Ad5‐hACE2 mice and CAG‐hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS‐CoV‐2 researches. The similarities or differences among the model‐specific pathologies may help in better understanding the pathogenic process of SARS‐CoV‐2 infection and aiding in the development of effective medications and prophylactic treatments for SARS‐CoV‐2. Highlights: We systematically describe and compare the histopathological changes at acute stage of the four types of SARS‐CoV‐2 infection hACE2 mouse models, which provides a framework that may help in better understanding the pathogenic process of SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain (RBD, residues 319–541) and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice. The antibodies also effectively suppressed SARS-CoV-2 RBD binding to soluble ACE2, indicating that RBD-mFc may be further developed as a safe and effective SARS-CoV-2 vaccine. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) Escherichia coli poses a great challenge for public health in recent decades. Polymyxins have been reconsidered as a valuable therapeutic option for the treatment of infections caused by MDR E. coli. A plasmid-encoded colistin resistance gene mcr-1 encoding phosphoethanolamine transferase has been recently described in Enterobacteriaceae. In this study, a total of 123 E. coli isolates obtained from patients with diarrheal diseases in China were used for the genetic analysis of colistin resistance in clinical isolates. Antimicrobial resistance profile of polymyxin B (PB) and 11 commonly used antimicrobial agents were determined. Among the 123 E. coli isolates, 9 isolates (7.3%) were resistant to PB and PCR screening showed that seven (5.7%) isolates carried the mcr-1 gene. A hybrid sequencing analysis using single-molecule, real-time (SMRT) sequencing and Illumina sequencing was then performed to resolve the genomes of the seven mcr-1 positive isolates. These seven isolates harbored multiple plasmids and are MDR, with six isolates carrying one mcr-1 positive plasmid and one isolate (14EC033) carrying two mcr-1 positive plasmids. These eight mcr-1 positive plasmids belonged to the IncX4, IncI2, and IncP1 types. In addition, the mcr-1 gene was the solo antibiotic resistance gene identified in the mcr-1 positive plasmids, while the rest of the antibiotic resistance genes were mostly clustered into one or two plasmids. Interestingly, one mcr-1 positive isolate (14EC047) was susceptible to PB, and we showed that the activity of MCR-1-mediated colistin resistance was not phenotypically expressed in 14EC047 host strain. Furthermore, three isolates exhibited resistance to PB but did not carry previously reported mcr -related genes. Multilocus sequence typing (MLST) showed that these mcr-1 positive E. coli isolates belonged to five different STs, and three isolates belonged to ST301 which carried multiple virulence factors related to diarrhea. Additionally, the mcr-1 positive isolates were all susceptible to imipenem (IMP), suggesting that IMP could be used to treat infection caused by mcr-1 positive E. coli isolates. Collectively, this study showed a high occurrence of mcr-1 positive plasmids in patients with diarrheal diseases of Guangzhou in China and the abolishment of the MCR-1 mediated colistin resistance in one E. coli isolate. [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica serovar Typhimurium is the most important serovar associated with human salmonellosis worldwide. Here we aimed to explore the molecular epidemiology and genetic characteristics of this serovar in Guangdong, China. Methodology: We evaluated the molecular epidemiology and genetic characteristics of 294 endemic Salmonella Typhimurium clinical isolates which were collected from 1977 to 2011 in Guangdong, China, and compared them with a global set of isolates of this serovar using epidemiological data and Multilocus Sequence Typing (MLST) analysis. Principal Finding: The 294 isolates were assigned to 13 Sequencing types (STs) by MLST, of which ST34 and ST19 were the most common in Guangdong. All the STs were further assigned to two eBurst Groups, eBG1 and eBG138. The eBG1 was the major group endemic in Guangdong. Nucleotide and amino acid variability were comparable for all seven MLST loci. Tajima’s D test suggested positive selection in hisD and thrA genes (p<0.01), but positive selection was rejected for the five other genes (p>0.05). In addition, The Tajima’s D test within each eBG using the global set of isolates showed positive selection in eBG1 and eBG138 (p<0.05), but was rejected in eBG243 (p>0.05). We also analyzed the phylogenetic structure of Salmonella Typhimurium from worldwide sources and found that certain STs are geographically restricted. ACSSuT was the predominant multidrug resistance pattern for this serovar. The resistant profiles ACSSuTTmNaG, ACSSuTTmNa and ACSuTTmNaG seem to be specific for ST34, and ASSuTNa for ST19. Conclusion: Here we presented a genotypic characterization of Salmonella Typhimurium isolates using MLST and found two major STs are endemic in Guangdong. Our analyses indicate that genetic selection may have shaped the Salmonella Typhimurium populations. However, further evaluation with additional isolates from various sources will be essential to reveal the scope of the epidemiological characteristics of Salmonella Typhimurium in Guangdong, China. [ABSTRACT FROM AUTHOR]

Toxigenic conversion of environmental V ibrio cholerae strains through lysogenic infection by the phage CTXΦ is an important step in the emergence of new pathogenic clones. The precursor form of the CTXΦ phage, pre- CTXΦ, does not carry the cholera toxin gene. During our investigation, we frequently found pre- CTXΦ prophages in non-toxigenic isolates in the serogroups of O1 and O139 strains in the Zhujiang estuary. We observed high amounts of sequence variation of rstR and gIIICTX in the pre- CTXΦ alleles as well as in the tcpA sequences within the strains. In addition, a new pre- CTXΦ allele, with a novel rstR sequence type and hybrid RS2, was identified. Our findings show that active, complicated gene recombination and horizontal transfer of pre- CTXΦs occurs within V . cholerae environmental strains, which creates a complex intermediate pool for the generation of toxigenic clones in the estuarine environment. [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica includes the major serovars associated with human salmonellosis. In this study, 1764 clinical Salmonella enterica isolates from diarrhea outpatients were collected from fifteen cities in Guangdong province, China, between 2007 and 2012. These isolates represent all of the Salmonella isolates collected from the province during that period.Methods: The isolates were characterized by serovar determination, antimicrobial susceptibility tests and PFGE fingerprint typing.Results: The serovar distribution results demonstrated that Salmonella Typhimurium (n=523, 29.65%) and Salmonella 4,5,12:i:- (n=244, 13.83%) are the most common serovars causing infant salmonellosis, whereas Salmonella Enteritidis (n=257, 14.57%) mainly causes human salmonellosis in adults. The serovar shift from Salmonella Enteritidis to Salmonella Typhimurium occurred in 2008. Antimicrobial susceptibility data showed a high burden of multidrug resistance (MDR) (n=1128, 56.58%), and a 20%-30% increase in the number of isolates resistant to ciprofloxacin (n=142, 8.05%) and third-generation cephalosporins (n=88, 4.99%) from 2007-2012. Only 9.97% of isolates (n=176) were fully susceptible to all agents tested. A high burden of MDR was observed in Salmonella Typhimurium and Salmonella 4,5,12:i:- for all age groups, and a reduced susceptibility to third-generation cephalosporins and quinolones occurred particularly in infants (≤ 6 years). The dominant PFGE patterns were JPXX01.GD0004, JEGX01.GD0006-7 and JNGX01.GD0006-7. ACSSuT was the predominant MDR profile in the Salmonella Typhimurium & 4,5,12:i:- complexes, while ASSuT-Nal and ASSu-Nal were the major MDR profiles in Salmonella Enteritidis. The predominant PFGE patterns of the Salmonella Typhimurium & 4,5,12:i:- complexes and Salmonella Stanley were most prevalent in infants (≤ 6 years). However, no obvious relationship was observed between these PFGE profiles and geographic location.Conclusions: These data reveal the serovar distribution of isolates recovered from diarrhea patients, the characteristics of resistant strains and fingerprint typing in Guangdong from 2007 to 2012. These results highlight a serovar shift and a worrying percentage of MDR strains with increasing resistance to quinolones and third-generation cephalosporins. Thus, continued surveillance of Salmonella and their MDR profiles using combined molecular tools and efforts to control the rapid increase in antimicrobial resistance among Salmonella in Guangdong are needed. [ABSTRACT FROM AUTHOR]

The aim was to understand persistence of the virus in body fluids the and immune response of an infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus disease 2019 (COVID-19). We determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction, serum antibodies of IgA, IgG and IgM by enzyme-linked immunosorbent assay and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China. We found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3 × 106 vs 6.4 × 104, p < 0.05; 7∼8 weeks) and throat (6.9 × 106 vs 2.9 × 105, p < 0.05; 4∼5 weeks), but similar in sputum samples (5.5 × 106 vs 0.9 × 106, p < 0.05; 4∼5 weeks). Viraemia was rarely detected (2.8%, n = 1/35). We detected early seroconversion of IgA and IgG at the first week after illness onset (day 5, 5.7%, n = 2/35). Neutralizing antibodies were produced in the second week, and observed in all 35 included cases after the third week illness onset. The levels of neutralizing antibodies correlated with IgG (r s = 0.85, p < 0.05; kappa = 0.85) and IgA (r s = 0.64, p < 0.05; kappa = 0.61) in severe, but not mild cases (IgG, r s = 0.42, kappa = 0.33; IgA, r s = 0.32, kappa = 0.22). No correlation with IgM in either severe (r s = 0.17, kappa = 0.06) or mild cases (r s = 0.27, kappa = 0.15) was found. We revealed a prolonged shedding of virus RNA in the upper respiratory tract, and evaluated the consistency of production of IgG, IgA, IgM and neutralizing antibodies in COVID-19 cases. Image 1 [ABSTRACT FROM AUTHOR]