Hydrophilic/hydrophobic characters of antimicrobial peptides derived from animals and their effects on multidrug resistant clinical isolates

Multidrug resistant（MDR） pathogen infections are serious threats to hospitalized patients because of the limited therapeutic options. A novel group of antibiotic candidates, antimicrobial peptides（AMPs）, have recently shown powerful activities against both Gram-negative and Gram-positive bacteria. Unfortunately, the viability of using these AMPs in clinical settings remains to be seen, since most still need to be evaluated prior to clinical trials and not all of AMPs are potent against MDR clinical isolates. To find a connection between the characteristics of several of these AMPs and their effects against MDR pathogens, we selected 14 AMPs of animal origin with typical structures and evaluated their in vitro activities against clinical strains of extensive drugresistant Acinetobacter baumannii, methicillinresistant Staphylococcus aureus, extended spectrum β-lactamase-producing Pseudomonas aeruginosa and extended spectrum β-lactamase-producing Escherichia coli. Our results showed that these peptides＇ hydrophilic/hydrophobic characteristics, rather than their secondary structures, may explain their antibacterial effects on these clinical isolates. Peptides that are amphipathic along the longitudinal direction seemed to be effective against Gramnegative pathogens, while peptides with hydrophilic terminals separated by a hydrophobic intermediate section appeared to be effective against both Gramnegative and Gram-positive pathogens. Among these, cathelicidin-BF was found to inhibit all of the Gram-negative pathogens tested at dosages of no more than 16 mg/L, killing a pandrug-resistant A. baumannii strain within 2 h at 4×MICs and 4 h at 2×MICs. Tachyplesin III was also found capable of inhibiting all Gram-negative and Gram-positive pathogens tested at no more than 16 mg/L, and similarly killed the same A. baumannii strain within 4 h at 4×MICs and 2×MICs. These results suggest that both cathelicidin-BF and tachyplesin III are likely viable targets for the development of AMPs for clinical uses.

Regeneration of islet β-cells in tree shrews and rats

Backgroud: Current understanding of injury and regeneration of islet β-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of β-cells in tree shrews.Methods: In this study, we examined the changes in islet cell composition and regeneration of β-cells after streptozotocin(STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet β-cells were observed using hematoxylin and eosin(HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1.Results: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet β-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet β-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed.Conclusion: The results suggest that the repair mechanism of islet β-cells in tree shrews is similar to that of humans.

SARS-CoV-2: Vaccines in the pandemic era

Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.

Reducing Viral Inhibition of Host Cellular Apoptosis Strengthens the Immunogenicity and Protective Efficacy of an Attenuated HSV-1 Strain

Herpes simplex virus 1(HSV-1),a member of a herpesviruses,shows a high infectivity rate of 30%-60%in populations of various ages.Some herpes simplex(HSV)vaccine candidates evaluated during the past 20 years have not shown protective efficacy against viral infection.An improved understanding of the immune profile of infected individuals and the associated mechanism is needed.HSV uses an immune evasion strategy during viral replication,and various virus-encoded proteins,such as ICP47 and Vhs,participate in this process through limiting the ability of CD8+cytotoxic T lymphocytes to recognize target cells.Other proteins,e.g.,Us3 and Us5,also play a role in viral immune evasion via interfering with cellular apoptosis.In this work,to study the mechanism by which HSV-1 strain attenuation interferes with the viral immune evasion strategy,we constructed a mutant strain,M5,with deletions in the Us3 and Us5 genes.M5 was shown to induce higher neutralizing antibody titers and a stronger cellular immune response than our previously reported M3 strain,and to prevent virus infection more effectively than the M3 strain in an in vivo mouse challenge test.

Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern

Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2.To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants,we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine,followed by challenging with emerging SARS-CoV-2 variants of concern(VOCs).

A comparative study of the characteristics of two Coxsackie A virus type 16 strains (genotype B)

Coxsackie A virus is one of the major pathogens associated with hand, foot and mouth disease (HFMD). The etiological characteristics of Coxsackie A virus type 16 (CA16) are thought to correlate with the pathological process of its infection. Two CA16 strains that were isolated from a severe HFMD patient presented with different plaque forms. This observation, along with biological analysis, indicated that the differences in the strains' biological characteristics, such as proliferation kinetics and immunogenicity, correlate with differences in their pathogenicity toward neonatal mice. Furthermore, these differences are thought to be associated with the sequence of the 5′ non-coding region of the viral genome and the VP1 structural region sequence. The results suggest that the biological and genetic characteristics of the CA16 viral strains are relevant to their pathogenicity.

Rapidly developable therapeutic-grade equine immunoglobulin against the SARS-CoV-2 infection in rhesus macaques

Dear Editor,The unprecedented COVID-19 pandemic caused by SARS-CoV-2 remains ongoing,but there is a lack of fully effective treatments.Convalescent plasma-derived hyperimmune globulins have been a safe and effective treatment but restricted by the difficulties in obtaining sufficient plasma with high antibody titers from a large number of recovered patients.Heterologous antibodies,particularly equine antibodies,have been widely used for decades as the therapeutics against some viral infections or as antivenoms.1 Equine antibodies could be rapidly developed and manufactured into therapeutic antibodies in large quantities under WHO standardized guidelines.Here we explored the development of equine antibody-derived F(ab′)2 as an option to treat COVID-19 by targeting the receptor-binding domain(RBD)of the viral spike protein that is essential for the viral entry into the host cells.2 We observed excellent neutralization titers of the F(ab′)2 in vitro and high potency against SARS-CoV-2 infection in the nonhuman primate rhesus macaques.