Member Info for inanaco

which is why a level playing field with "Gov cash" is so important

funny was looking at that as well .........

an example of why "High Avidity" is so important ....

Out of 28 residues in the epitope (defined as residues buried by CR3022), 24 (86%) are conserved between SARS-CoV-2 and SARS-CoV (Figs. 1D and 2A). This high sequence conservation explains the cross-reactivity of CR3022. Nonetheless, despite having a high conservation of the epitope residues, CR3022 Fab binds to SARS-CoV RBD [dissociation constant (Kd) = 1 nM] with a much higher affinity than it does to SARS-CoV-2 RBD (Kd = 115 nM) (Table 1 and fig. S3). The difference in binding affinity of CR3022 to SARS-CoV-2 and SARS-CoV RBDs is likely due to the nonconserved residues in the epitope (Fig. 2). The most drastic difference is an additional N-glycosylation site at N370 on SARS-CoV (N357 in SARS-CoV numbering). The N-glycan sequon (N-X-S/T, where X is any amino acid but proline) arises from an amino acid difference at residue 372, where SARS-CoV has a Thr compared with Ala in SARS-CoV-2 (Fig. 2B). Mass spectrometry analysis shows that a complex glycan is indeed present at this N-glycosylation site in SARS-CoV (8). An N-glycan at N370 would fit into a groove formed between heavy and light chains (Fig. 2C), which could increase contact and thus binding affinity to CR3022. This result also suggests that the difference in antigenicity between the RBDs of SARS-CoV-2 and SARS-CoV can be at least partially attributed to the N-glycosylation site at residue 370. We tested whether CR3022 was able to neutralize SARS-CoV-2 and SARS-CoV in an in vitro microneutralization assay (7).

""""""""""Although CR3022 could neutralize SARS-CoV, it did not neutralize SARS-CoV-2 at the highest concentration tested (400 µg/ml) (fig. S4). This in vitro neutralization result is consistent with lower affinity binding of CR3022 for SARS-CoV-2, although other explanations are also possible, as outlined below."""""""""

While N protein may not be able to elicit an effective neutralizing antibody response against live SARS-CoV, we have shown that it is capable of eliciting a SARS-CoV antigen-specific CD8+ T-cell response that results in a significant reduction of titer of challenging vaccinia virus when linked to CRT in a DNA vaccine.

DNA vaccination.
DNA-coated gold particles were prepared according to a previously described protocol (6). DNA-coated gold particles were delivered to the shaved abdominal regions of mice using a helium-driven gene gun (Bio-Rad) with a discharge pressure of 400 lb/in2. C57BL/6 mice were immunized with 2 µg of the plasmid encoding no insert, CRT, N, or CRT/N protein. The mice received two boosters with the same dose at a 1-week interval.

this was work done in 2004 ............ DNA vaccine against the N ...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC387705/

Wild it defiantly shows that the spike proteins are pretty different between sars and covid ...

who else is going after the N Protein ? just looking now ..

another issue i have found ....

Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to non-neutralizing antibodies enhances its entry into host cells, and sometimes also its replication.[1] This phenomenon—which leads to both increased infectivity and virulence—has been observed with mosquito-borne flaviviruses such as Dengue virus, Yellow fever virus and Zika virus,[2][3] with HIV, and with coronaviruses.

There are various hypotheses on how ADE happens and there is a likelihood that more than one mechanism exists. In one such pathway, some cells of the immune system lack the usual receptors on their surfaces that the virus uses to gain entry, but they have Fc receptors that bind to one end of antibodies. The virus binds to the antigen-binding site at the other end, and in this way gains entry to and infects the immune cell. Dengue virus can use this mechanism to infect human macrophages, if there was a preceding infection with a different strain of the virus, causing a normally mild viral infection to become life-threatening.[4]

An ongoing question in the COVID-19 pandemic is whether—and if so, to what extent—COVID-19 receives ADE from prior infection with other coronaviruses.[5]

ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. Vaccine candidates for Dengue virus and feline infectious peritonitis virus (a cat coronavirus) had to be stopped because they elicited ADE.[6]

just looking at the spike as you posted ... (I will read your post now wild)

but from his point of view ( working with Scancell)

https://www.nottingham.ac.uk/life-sciences/people/christopher.coleman

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important because of the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4, and type 2 diabetes was induced by administering a high-fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery that was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation, which was then prolonged through 21 days after infection. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells, which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response, which results in more severe and prolonged lung pathology.

https://insight.jci.org/articles/view/131774

https://www.sciencedirect.com/science/article/pii/S0264410X17301937?via%3Dihub

seems the "Gulf" is not as far apart as some think ...

the Expert

https://www.channel4.com/news/quarantine-is-unimplementable-and-completely-ineffective-ryanair-boss-michael-oleary

Does being exposed to more coronavirus particles mean you will develop a more severe illness? Rumours circulating on social media suggest that hospital workers or their household members exposed to a higher “viral load” become sicker than the general population. But emerging research indicates the relationship between infection and covid-19 severity may be more complex – and differ from that of other respiratory illnesses.

The average number of viral particles needed to establish an infection is known as the infectious dose. We don’t know what this is for covid-19 yet, but given how rapidly the disease is spreading, it is likely to be relatively low – in the region of a few hundred or thousand particles, says Willem van Schaik at the University of Birmingham, UK.

Viral load, on the other hand, relates to the number of viral particles being carried by an infected individual and shed into their environment. “The viral load is a measure of how bright the fire is burning in an individual, whereas the infectious dose is the spark that gets that fire going,” says Edward Parker at the London School of Hygiene and Tropical Medicine.

Read more: https://www.newscientist.com/article/2238819-does-a-high-viral-load-or-infectious-dose-make-covid-19-worse/#ixzz6NF0XPMoC

The biggest issue with masks is ...

when wet will people change them probably every 20 mins ... once wet the mask creates a barrier to air so the air leaks and follows the path of least resistance .. if you then cough you force air through a heavily contaminated "wet patch" actually adding to the viral load of the cough

If you reposition the mask with your hands , you have just touched a heavily viral loaded wet patch you then touch another surface'

so the testing with fans and cages does not reflect what happens in real life ..

will they wear them correctly ?

how many times on TV do you see the policeman wearing a mask below the nose ?

its a very difficult area to enforce or to make sure the mask you are using are approved

because you have

1/ weather ....... affects it enormously , humidity and temperature
2/ Cost ....
3/ how long could you can tolerate the mask
4/ is it Correctly worn because this is you trying to protect somebody else ... so somebody else has to trust those that wear the mask correctly to close up social distancing on public transport ?
4/ is it changed as it becomes a Hot wet breeding ground for bacteria etc
5/ surgical cloves and a visor are required to protect you ie full PPE

yes and it means you need potent t cells from a vaccine then ................ if you are having to using Il7 to boost t cells developed from a viral challenge

IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development.[15] This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes.[citation needed] Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.[1

COVID-19-specific animal models are being developed, including ACE2-transgenic mice, hamsters, ferrets and non-human primates. Biosafety-level 3 containment measures are needed for animal studies involving live-virus challenges, and the demand for these capabilities is likely to require international coordination to ensure that sufficient laboratory capacity is available

https://www.nottingham.ac.uk/safety/documents/bio-gm-cl3-policy.pdf

Ruck you posted

"As far as funds go, it doesn't take a genius to work out when the money is likely to run out."

then why ask one ....

LOL

you did not read my reply

"" its not up to me to crystal ball what BOD have planned ""

Try the Fair ... you may discover the Knowlesi tent .... brightly covered sometimes wooden, possible horse, parked outside

simple response back ....... Ruck

Scancell is a research based company that at the moment is funded by the stock market ....

if you don't like that model ... why invest in shares that are currently using that model ... ?

if live was easy ... Covid would not have appeared ...

Business adapts ...

Professor Karol Sikora
@ProfKarolSikora
Why are we not seeing more positive antibody results?

A paper in 'Cell' suggests that T lymphocytes are our main defence.

There could be significant cross-immunity from 'common cold' coronaviruses which provide protection.

Very important - we need a better test for immunity.

its not up to me to crystal ball what BOD have planned ..

and your attempts at if have proved wrong and me for that matter ....... your last buy 10p 3 years ago

mine 7.7p ...

however i have bought plenty before sub 10p ... as well with the lowest 3.9p (which you was critical off)

position ... over 3/4 million now ..

happy to wait ... happy to hold ...

Ruck ...

some have a vested interest to see the SP above 22p ......... in approx 9 weeks

Professor Lindy Durrant, Chief Scientific Officer and Professor of Cancer Immunotherapy at the University of Nottingham, in collaboration with scientists in the newly established Centre for Research on Global Virus Infections and the new Biodiscovery Institute at the University of Nottingham, and Nottingham Trent University1.

so a lot of "help" is available on the testing side ....

a lot of the preparatory work has already been done on the SCIB2 and SCIB1 trial procedure, so its far easier to add an immunobody vaccine to the pipeline.
you are only changing epitopes ...
so i see little impact on the rest of the pipeline once the epitopes have been selected by virologists not Scancell and inserted into the construct by scancell , from then on its test test test