Impacts of SARS-CoV-2 Omicron variant on Infectivity, Vaccine breakthrough, and Antibody resistance

A group from Department of Mathematics, Michigan State University, MI, USA, etc. has reported on Infectivity, vaccine breakthrough, and antibody resistance of SARS-CoV-12 Omicron variant.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647651/

Infectivity:
The Infectivity of SARS-CoV-2 is mainly determined by the binding affinity of the ACE2 and RBD complex, although the furin cleavage site plays a crucial role as well. Omicron has three mutations at the furin cleavage site and 15 mutations on the RBD, suggesting a significant change in its infectivity. Changes in the infectivity of Omicron were analyzed by examining the Binding free energy (BFE) changes of the ACE2 and S protein complex induced by 15 Omicron RBD mutations. As a result, Omicron is to be about 2.8 times as infectious as the Delta (i.e., BFE change: 1.57kcal/mol).

Vaccine breakthrough:
A molecule-based data-driven analysis as done about Omicron’s impact on vaccines through a library of 132 known antibody and S protein complexes. Changes in the binding free energy induced by 15 RBD mutations on these complexes were evaluated to understand the potential impact of Omicron’s RBD mutations to vaccines. This study does not include a few known antibody-S protein complexes that are far away from the RBD, such as those in the N-terminal domain (NTD), due to limited experimental data in the antibody library. As a result, Omicron’s vaccine-escape capability will be about twice as high as that of the Delta variant.

Antibody resistance:
Omicron will have a very mild negative impact on the Regeneron cocktail.

Glycan profile of Schistoeoma mansoni EVs and those origins: Importance of α-6 Sialic acids

A group from Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, QC, Canada, etc. has reported on glycan profile of Schistoeoma mansoni EVs and those origins.
https://www.mdpi.com/2076-0817/10/11/1401/htm

Using lectin microarrays, it was identified several lectins that exhibit strong adhesion to Schistosoma mansoni EVs, suggesting the presence of multiple glycan structures on these vesicles. Interestingly, SNA-I, a lectin that recognises structures with terminal α2-6 sialic acid, displayed strong affinity for S. mansoni EVs. SNA-II and RCA-I, which have affinity for structures which are frequently terminated with sialic acids showed strong intensities as well. In addition, the four mannose-binding lectins, Calsepa, NPA, GNA and HHA, showed strong intensities, suggesting abundance of high-mannose glycans.

Question is the origin of sialic acid.
To identify worm structure(s) as possible sources of EVs, we performed histochemistry on whole adult worms with three lectins that exhibited strong affinity for S. mansoni EVs (DSA, RCA-I and SNA-I). 100% of tegumental cells are positive for SNA-I labelling, DSA labels definitive tegumental cells and the gut of the parasite, and RCA-I labelled various structures within the worm, including potential tegumental cells and what appear to be the excretory pore and excretory tubules. Together, these results may indicate the presence of multiple EV sub-populations and the involvement of the tegument and the digestive and protonephridial (excretory) systems in the release of EVs from adult schistosomes.

This finding on glycosylation profile of Schistosoma mansoni EVs and those origins is of interest, as sialic acids play important roles in the context of infection by aiding immune evasion, affecting target recognition, cell entry, etc.

Titanium (Ti) foliar application promotes plant growth by Phosphorus (P) uptake through in root auxin content and photosynthetic efficiency

A group from College of Agronomy, Sichuan Agricultural University, Chengdu, China, etc. has reported that Titanium (Ti) foliar application increases Phosphorus (P) uptake through in root auxin content and photosynthetic efficiency.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631872/

Under normal light (NL), photosynthetic Rate increased significantly in response to T2 (14.06%) and T3 (30.46%) against T0 (control) in High P condition, whereas in Low P condition, a significant increase was recorded in T2 (21.98%), T3 (38.81%), and T4 (21.43%) as compared to control, where T0, T1, T2, T3 and T4 mean different concentrations of Ti (T0 = 0, T1 = 125, T2 = 250, T3 = 500 and T4 = 1,000 mg/L), and high P (HP) = 100 mg/kg and low P (LP) = 10 mg/kg.

It was found that the increase in root growth traits such as root hairs, root length, lateral root formation and root surface area was associated with root auxin content. This increase in the morphological characteristics of roots due to the Auxin content significantly improved the efficiency of nutrient absorption, for example P.

Effect of Ti application on (A) root length, (B) root surface area, (C) root volume, and (D) root diameter of soybean under NL and shade (SC) combined with Low P and High P conditions.

Lipid nanoparticle (LNP) enhances the efficacy of mRNA vaccines as a versatile adjuvant

A group from Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA has shown that Lipid nanoparticle (LNP) enhances the efficacy of vaccines as a versatile adjuvant using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566475/

Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. LNP-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized.

To demonstrate that this LNP formulation can provide adjuvant activity for other antigens, empty LNP (eLNP)- and AddaVax-adjuvanted SARS-CoV-2 spike protein subunit vaccines were evaluated using mice. Mice were immunized with a single dose of recombinant SARS-CoV-2 spike protein receptor binding domain (rRBD) adjuvanted with eLNP or AddaVax. As a positive control, another group of mice was immunized with nucleoside-modified RBD mRNA-LNP. It was found that LNP-adjuvanted vaccines elicited durable RBD-specific IgG titers that were significantly higher than the AddaVax-elicited responses.

To evaluate the adjuvant properties of LNPs with and without the ionizable lipid, mice were immunized with hemagglutinin recombinant protein (rHA) mixed with the two different formats of eLNP. The eLNP with the ionizable lipid showed high hemagglutinin inhibition titers, however, strikingly, eLNP not containing the ionizable lipid did not possess adjuvant activity.

IL-6 has been shown to be an early regulator of T follicular helper (Tfh) cell differentiation. Tfh cells are a subset of CD4+ T cells specialized in regulating affinity maturation of B cells in germinal centers (GCs). Induction of Tfh cells is critical for durable, protective Ab responses. It was found that the eLNP containing the ionizable lipid (eLNP) and mRNA-LNP induced large amounts of proinflammatory cytokines and chemokines, whereas the LNP lacking the ionizable lipid and AddaVax elicited lower cytokine and chemokine concentrations.

where, empty LNP (eLNP), AddaVax (an MF59-like adjuvant).

Effects of flooding on spring wheat rhizosphere

A group from Microbial Biogeochemistry, Research Area Landscape Functioning, Leibniz Center for Agricultural Landscape Research e.V., Müncheberg, Germany, etc. has reported effects of flooding on spring wheat rhizosphere.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602104/

Flooding caused followings,
(i) significant increase of bacterial taxa with anaerobic respiratory capabilities, such as members of Firmicutes and Desulfobacterota,
(ii) a significant reduction in Actinobacteria and Proteobacteria,
(iii) depletion of several putative plant-beneficial taxa, and
(iv) increases of the abundance of potential detrimental bacteria.

To be more specific, flooding promoted an enrichment of the genera Geobacter and Clostridium. It is known that several Clostridium species might cause soft rot disease in several vegetable crops and their abundance significantly increased with heavy rainfall and flooding. On the other hand, a dramatic reduction of the abundance of Streptomyces and Spinghomonas occurred in all flooding samples, which have been described as beneficial for wheat growth. Members of these two genera, are able to solubilize inorganic phosphorus, to form siderophores and affect phytohormones production and might be involved in biocontrol activity.

Bacteria affiliated to the genus Saccharimonadia, which shows putative beneficial features such as improving nitrogen uptake efficiency and promoting nutrient conversion, were mainly depleted in flooded roots. A similar trend was observed in the rhizosphere for families Rhizobiaceae and Xanthobacteraceae.

Members of different Massilia species are considered as putatively plant-beneficial (in terms of producing proteases, sidephores and the auxin indole-3-acetic acid). Massilia ASVs were significantly more abundant in the control roots of young plants, but they were not detected in those of the flooded ones. Likewise, the flooded wheat roots at booting stage revealed a significant reduction of Flavobacterium ASVs, which are known for plant growth promoting traits. Bacteria of this genus have the capabilities to solubilize phosphate, use of 1-amino cyclopropan-1-carboxylate as sole nitrogen source and production of auxin, siderophores, salicylic acid, antifungal chitinases and hydrogen cyanide.

In summary, these findings demonstrated that flooding significantly altered negatively the assemblage dynamics of the root microbiota, with a significant depletion of putatively beneficial bacterial taxa associated with the root and rhizosphere of spring wheat plant.

Relationship between SARS-CoV-2 mutations and those related concerns

A group from University of Florida College of Medicine, Gainesville, FL, USA, has summarized relationship between SAS-CoV-2 mutations and those related concerns.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606318/

Mutations in the RBD
RBD mutations (such as K417 N, L452R, E484K) have the potential to influence neutralizing antibody binding. One RBD mutation, N501Y, was shown to increase the affinity of the spike protein for the host receptor ACE2. These advantageous mutations acquired in the spike protein S1 NTD and RBD possibly enhance receptor/co-receptor binding.

Mutations in the NTD
Although it is clear why mutations in the RBD have the potential to change virus fitness (by altering neutralizing antibody and host cell ACE2 binding), it is not clear why advantageous distinguishing mutations are emerging in the NTD. Since SARS-CoV-2 elicits neutralizing antibodies that bind multiple epitopes on the spike protein, including the NTD, it is very much likely that the NTD participates in an important but unknown function related to virus fitness (e.g., co-receptor binding).

Mutations at interchain contacts in the spike protein trimer
A570D, D614G, A701V, D950 N, and S982A are located at interchain contact sites. The substitutions at spike trimer interfaces likely reduce intermolecular binding affinity. These acquired mutations likely destabilize the spike protein in a manner that enhances dynamic virus processes including spike protein cleavage, structural rearrangement and host cell fusion mechanisms.

Mutations in the furin cleavage site
Mutations in position 681 of the spike protein can be seen in the highly transmissible alpha and delta variants, but not less transmissible variants of concern, beta and gamma. Position 681 is located adjacent to the RRAR proprotein convertase motif (furin cleavage site) considered a hallmark of high pathogenesis. Since endosomal S1/S2 cleavage occurs in an acidified environment, positively charged amino acids at position 681 in highly transmissible variants (H in alpha, R in delta) have the potential to influence the rate of spike protein cleavage and subsequent membrane fusion mechanisms to gain cell entry.