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https://jvi.asm.org/content/94/18/e01279-20
LETTER
Dutta and coworkers suggest in a recent letter (1) that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (N) might be a good vaccine target. They argue that the conserved nature of the N protein makes it a suitable vaccine component. The concept of using a nucleoprotein to protect against infection was already shown in chimpanzees in 1985 when Iwarson and colleagues used the hepatitis B core antigen to protect chimpanzees against hepatitis B challenge (2). A SARS-CoV-2 infection in macaques protects against reinfection, supporting the concept of a protective immunity (3), and an inactivated whole-virus vaccine, containing all structural proteins of SARS-CoV-2, protects macaques against infection (4). However, the vast majority of vaccines currently in clinical development are based only on the spike protein, or parts thereof, and seem to protect against disease but not against infection (5, 6). When these are based on viral vectors, antivector immunity limits repeat vaccinations. We agree with Dutta and colleagues on the importance of the N protein in vaccines and show data to support this view. The partners in the OPENCORONA vaccine consortium generated a codon-optimized SARS-CoV-2 N gene based on the Wuhan-1 isolate (7) (GenScript, USA). A final SARS-CoV-2 vaccine combines the N protein with other structural proteins to generate a synthetic whole-virus vaccine. To first test that a SARS-CoV-2 N plasmid is safe and immunogenic in a larger animal, we immunized six New Zealand White rabbits with 0.3 or 0.9?mg of DNA intramuscularly (i.m.) at weeks 0 and 3 using in vivo electroporation (EP) (GeneDrive; IGEA, Italy). Venous blood was drawn at weeks 2 and 5 and was analyzed for the presence of N antibodies by an in-house enzyme-linked immunosorbent assay (ELISA) (8) using an Escherichia coli-expressed N protein based on the same strain (GenScript). A single injection of the N plasmid induced anti-N titers of 103 to 104, and 2 weeks after a boost the levels reached 104 to 105, with no difference in the DNA dose used (Fig. 1). Thus, the SARS-CoV-2 N gene was safe and highly immunogenic as a DNA vaccine. To evaluate the ability of the SARS-CoV-2 N DNA to induce T cells, and in particular T cells cross-reacting with coronaviruses (CoVs) from other species, we immunized groups of C57BL/6 mice with N protein in adjuvant (data not shown) or 50?µg of DNA. Splenocytes were analyzed for recognition of N-based peptide pools containing four overlapping peptides by enzyme-linked immunospot (ELISpot) assay as described previously (8). This revealed a single region to which H-2b-restricted T cells produced both interleukin-2 (IL-2) (data not shown) and gamma interferon (IFN-?) (Fig. 1). Importantly, the sequence of this region was 100% identical to that of pangolin CoV and had an 86% homology with that of bat CoV.
anyway impressed with Synair .. and if i had space in my ISA i would include them, however Scancell is a way bigger player with its potential from a returns point of view ..
that was the bit i was after...
""" All interferons significantly enhance the presentation of MHC I dependent antigens"""
so synair could act as a primer for an adaptive response
got it now ........
All interferons share several common effects: they are antiviral agents and they modulate functions of the immune system. Administration of Type I IFN has been shown experimentally to inhibit tumor growth in animals, but the beneficial action in human tumors has not been widely documented. A virus-infected cell releases viral particles that can infect nearby cells. However, the infected cell can protect neighboring cells against a potential infection of the virus by releasing interferons. In response to interferon, cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 in response to new viral infections; the phosphorylated eIF-2 forms an inactive complex with another protein, called eIF2B, to reduce protein synthesis within the cell. Another cellular enzyme, RNAse L—also induced by interferon action—destroys RNA within the cells to further reduce protein synthesis of both viral and host genes. Inhibited protein synthesis impairs both virus replication and infected host cells. In addition, interferons induce production of hundreds of other proteins—known collectively as interferon-stimulated genes (ISGs)—that have roles in combating viruses and other actions produced by interferon.[12][13] They also limit viral spread by increasing p53 activity, which kills virus-infected cells by promoting apoptosis.[14][15] The effect of IFN on p53 is also linked to its protective role against certain cancers.[14]
Another function of interferons is to up-regulate major histocompatibility complex molecules, MHC I and MHC II, and increase immunoproteasome activity. All interferons significantly enhance the presentation of MHC I dependent antigens. Interferon gamma (IFN-gamma) also significantly stimulates the MHC II-dependent presentation of antigens. Higher MHC I expression increases presentation of viral and abnormal peptides from cancer cells to cytotoxic T cells, while the immunoproteasome processes these peptides for loading onto the MHC I molecule, thereby increasing the recognition and killing of infected or malignant cells. Higher MHC II expression increases presentation of these peptides to helper T cells; these cells release cytokines (such as more interferons and interleukins, among others) that signal to and co-ordinate the activity of other immune cells
https://en.wikipedia.org/wiki/Interferon#:~:text=A%20virus%2Dinfected%20cell%20releases,protein%20kinase%20R%20(PKR).
there are 4 or 5 interferon ...the original article did not specify .
that synair data is impressive not studied beta, but i suspect the immune system responds also to that call for help .. cytokine
which is what Gamma does ... which also has the same anti viral effect
so this Vax is showing strong Bias of its CD4 to .. Th1
https://ir.novavax.com/news-releases/news-release-details/novavax-announces-positive-phase-1-data-its-covid-19-vaccine
NVX-CoV2373 induced neutralization titers in 100% of participants; 5 µg adjuvanted dose group peak GMT: 3,906 (95% CI: 2,556; 5,970).
All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID-19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.
Matrix-M™ adjuvant induced robust polyfunctional CD4+ T cell responses.
The adjuvant was dose-sparing, with the lower 5 µg dose of NVX-CoV2373 performing comparably with the 25 µg dose. Cellular immune responses were measured in a subset of participants, and NVX-CoV2373 induced antigen-specific polyfunctional CD4+ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a).
they are talking about ..... Interferon gamma (IFN?) this is what Scancell High Avidity T cells produce copious qty off ....
They are have whats called a Th1 profile ... this induces high inflammatory response (interferon)
actually it achieved the opposite ...... somebody very high up in Scancell was really miffed with the GOV. and that actually spurred them on ... I will not mention names . ... however they did describe the science as Brilliant
well that time also gave Innovate UK time to evaluate the proposal properly .. and clearly given scancell the time (funded by us) to develop that science while we waited for funding ... What we do know ... Scancell will not put forward inferior products because of Shareholder pressure that clearly has been proven over the last few years, so they would not develop a Covid under time constraints ie dead lines .... so again back to that principle ""get it right first time"" is far easier than going back to the drawing board ... phase 1 trail with pre-clinical has a cost of £2.7m ... get it wrong is expensive
Problem i have with that Video link provided ... on the Oxford vaccine and the way they are discussing a like for like antibody response to recovered Covid patients ..
Those Covid Patients have a comprehensive immune response to the Virus itself .... what they are not saying is that comprehensive response .. is replicated ... only part of it ...
For those that made a killing here ... Daily Mail is reporting that the current crop of 1st generation vaccines may not protect as well as might have been expected, ... 2nd generation vaccines going into trial soon might ... so who has it ?
read my history