A Rift Valley fever mRNA vaccine elicits strong immune responses in mice and rhesus macaques.

Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR(-/-) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.

An adenovirus-vectored RVF vaccine confers complete protection against lethal RVFV challenge in A129 mice.

Instruction: Rift valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that causes severe disease in animals and humans. Nevertheless, there are no vaccines applied to prevent RVFV infection for human at present. Therefore, it is necessary to develop a safe and effective RVFV vaccine. Methods: We generated Ad5-GnGcopt, a replication-deficient recombinant Ad5 vector (human adenovirus serotype 5) expressing codon-optimized RVFV glycoproteins Gn and Gc, and evaluated its immunogenicity and protective efficacy in mice. Results and Discussion: Intramuscular immunization of Ad5-GnGcopt in mice induces strong and durable antibody production and robust cellular immune responses. Additionally, a single vaccination with Ad5-GnGcopt vaccination can completely protect interferon-α/ß receptor-deficient A129 mice from lethal RVFV infection. Our work indicates that Ad5-GnGcopt might represent a potential vaccine candidate against RVFV. However, further research is needed, first to confirm its efficacy in a natural animal host, and ultimately escalate as a potential vaccine candidate for humans.

Trends and hotspots for European Journal of Medicinal Chemistry: A bibliometric study.

European Journal of Medicinal Chemistry (EJMC) has been around for a long time and has gained broad interest from the various individuals working in the field. However, there is no bibliometric analysis on the publications of EJMC to thoroughly assess the scientific output and current status systematically. Therefore, the study was conducted to analyze the various publications of EJMC from 1987 to 2022 to improve their quality. A total of 13,386 papers were retrieved, with the number of publications increasing yearly. Based on the multiple indicators of bibliometrics, the highest impact countries, institutions, authors and representative literature were identified, and visualization networks were constructed using VOSviewer. Keyword co-occurrence analysis reveals a gradual shift from phenotypic drug discovery to target-based drug discovery in the EJMC theme change. Moreover, further discussion of the keyword clustering results is provided to support researchers in defining the scope of their research topics and planning their research directions. At this stage, there is a greater focus on developing antitumor and oxidative stress-related drugs than on the earlier anti-infective activities. In future studies, the main research directions are tumor multidrug resistance, oxidative stress, and dual inhibitors.

Single-dose of a replication-competent adenovirus-vectored vaccine provides sterilizing protection against Rift Valley fever virus challenge.

Rift Valley fever virus (RVFV) is one of the most important virulent pathogens causing severe disease in animals and humans. However, there is currently no approved vaccine to prevent RVFV infection in humans. The use of human adenovirus serotype 4 (Ad4) as a vector for an RVFV vaccine has not been reported. Here, we report the generation of a replication-competent recombinant Ad4 vector expressing codon-optimized forms of the RVFV glycoproteins Gn and Gc (named Ad4-GnGc). Intramuscular immunization with Ad4-GnGc elicited robust neutralizing antibodies against RVFV and cellular immune responses in mice. A single low-dose vaccination with Ad4-GnGc completely protected interferon-α/ß receptor-deficient A129 mice from lethal RVFV infection. More importantly, Ad4-GnGc efficacy was not affected by pre-existing immunity to adenovirus serotype 5, which currently exists widely in populations. These results suggest that Ad4-GnGc is a promising vaccine candidate against RVFV.

[Preparation and biological activity analysis of chimeric antibody against capsular F1 antigen of Yersinia pestis].

OBJECTIVE: To express human-mouse chimeric antibody against Yersinia pestis F1 capsular antigen (F1 antigen) and analyze its biological activities. METHODS: The heavy chain gene of the chimeric antibody was obtained by fusing the variable region gene of the mouse mAb heavy chain with human IgG1 constant region gene. The light chain gene of the chimeric antibody was obtained by fusing the variable region gene of the mouse mAb light chain with the human kappa constant region gene. Both the heavy and light chain genes of the chimeric antibody were further verified by sequencing. The chimeric antibody heavy and light chain genes were inserted into EcoR I/Not I of pcDNA3.1 (+) to construct expression plasmids termed pcDNA3.1-L and pcDNA3.1-H, respectively. Then, two plasmids were mixed and transfected into CHO-S cells. Finally, the stable cell clone secreting chimeric antibody was obtained by G418 selection. The culture supernatants of serum-free medium were collected and the chimeric antibody was purified by MabSelect SuRe affinity chromatography. The purified chimeric antibody was analyzed by SDS-PAGE, Western blotting, ELISA and evaluated in the protective effect in vivo. RESULTS: PCR and sequencing analysis proved that plasmids pcDNA3.1-H and pcDNA3.1-L were correctly constructed. Dot blot showed that a cell line with high-level expression of chimeric antibody was obtained. SDS-PAGE and western blot showed that the chimeric antibody was successfully purified. ELISA showed that the chimeric antibody could specifically bind to F1 antigen. In vivo activity assay showed that 80% BALB/c mice treated with the chimeric antibody survived from 36 MLD virulent Yersinia pestis. CONCLUSION: The chimeric antibody against F1 antigen with neutralizing activity was successfully expressed in CHO-S cells, which laid a foundation for the preparation of anti-plague passive immunity agents.

[Study on a novel mutation of B glycosyltransferase gene related with an ABx variant].

OBJECTIVE: To explore the molecular basis of an individual featuring an ABx variant of ABO blood group system. METHODS: Serological assays were used to characterize the erythrocyte phenotypes and salivary ABH secretors. All of the seven exons and flanking introns of ABO glycosyltransferase gene were amplified with polymerase chain reaction (PCR). And the products were sequenced bidirectionally following enzyme digestion. Exons 6 and 7 were also subcloned and analyzed for haplotypes of the ABO gene. RESULTS: Erythrocytes of the proband have expressed a strong A antigen and a weak B antigen, which was identified as a rare ABx variant in addition with other serological features. Nine heterozygous sites in exon 6 (297A/G) and exon 7 (467C/T, 526C/G, 657C/T, 703G/A, 796C/A, 803G/C, 808T/A, 930G/A) of the coding region of the ABO gene were identified. Based on haplotype analysis, one allele was determined as common A102, whilst another was consistent with B101 except for an 808T>A mutation which has resulted in replacement of phenylalanine with isoleucine at position 270 of glycosyltransferase B. CONCLUSION: The 808T>A mutation of the glycosyltransferase B gene may decrease the enzymatic activity and result in the Bx variant.

[Molecular basis for real RhD negative and RhDel phenotypes in Yiwu population of Zhejiang Province in China].

This study was purposed to investigate the molecular basis for RhD negative phenotype in Yiwu population in Zhejiang Province of China. The RhD negative samples were screened by saline agglutination test in blood donors. Some real RhD negative and RhDel phenotypes were identified using anti-human globulin test and absorbtion elution test. Ten exons of RHD gene in these samples were amplified by PCR-SSP, and positive exons were DNA sequenced. The results indicated that 30 real RhD negative and 8 RhDel phenotypes were identified in 38 initial RhD negative samples. Ten exons were complete negative in 28 real RhD negative samples and only exon 1, 2 and 10 were positive in 2 real RhD negative samples amplified by PCR. All 10 exons in 8 RbDel samples were positive and a DNA variant (1227G > A) was found in 8 RhDel samples. It is concluded that all exons are absence in most real RhD negative phenotypes, and the partial exons absence is also found in some real negative phenotypes among Yiwu population in Zhejiang province of China. The G to A mutation at position 1227 is found in all RhDel phenotypes.