I'm going to try to delve Rich Purcell's presentation. He went knee deep in the weeds, was hard to hear, and speaks a bit monotone with no needed pauses to help the listener. I'm joking a bit here on him, but it's just fun because obviously I respect him. Thankfully he's a scientist and not a radio host!
I noticed he thanked a NGIO Advisory Board member named Thomas Rodgers. He thanked him for leading the antibody work done in the labs at UCSD. He has an impressive profile page at UCSD. I recall a recent article from Malaysia where Joe is quoted as saying a peer review for this work is authored by TF Rodgers. So here's our guy with the Ii-Key Covid/Sars peer review to soon be on this page:
https://profiles.ucsd.edu/thomas.rogers
Rich excited the listeners by enthusiastically noting Generex's partnership with EpiVax! He called them a partner in computational vaccinology that utilizes an algorithm to identify the best epitopes for a vaccine. Think of a dart board player that only throws bullseyes. So, out of thousands of epitopes found in the spike membrane proteins of the Corona virus, Generex and EpiVax selected 33 epitopes with the highest probability of being highly immunogenic. The team manufactured and tested those 33 at CTL "Cellular Technology Limited" (http://www.immunospot.com/about/about-immunospot) in Ohio.
Things got exciting as Rich mumbled about the T Cell Assay and Elispot Assay test for gamma interferon. This gamma interferon measures TH1, the good T Cell helper cells. The gang also measured for Enzyme B, which indicates the presense of CD8 killer cells. They tested for IL5 which indicated the trend towards TH2 the negative CD8 response that they don't want to see since that could bring around the potential for cytotoxic storm.
The suspense was building. Rich explained that Generex tested 46 blood samples for human patients that had covid. They tested 31 samples from patients that didn't have covid. Their samples were collected by Generex's partners in 2017/18. The goal was to see if the Ii-Key Covid vaccine was generating specific immune reactions against covid-19 rather than against normal human blood virus that may have been exposed to previous corona virus infections.
And we have our results. Joe needs to give Rich a Red Bull. Anyway, the results of the T Cell Assay show a positive reaction for CD4 TH1 response with gamma interferon. They show a positive response for CD8 killer T Cell. They show no indication at all with TH2 response from IL5 (pronounced aisle 5 like at WalMart.) That was the response hoped for across the board. As Rich stated, "we are very excited, the results are very encouraging." He sounded it! But seriously, this very good news.
These are the assay results we needed. They are completely positive. Evidently, TF Rodgers is writing the peer review.
The fun isn't over. Rich informed that the FDA requested a Immunogenicity study. Tension was in the air as he explained that a cytometric bead array to measure other cytokines measured by IL6, IL8 and CXCL9/MIG. Common topics people talk about every day. Rich explained that IL6 had good and bad effects that either early on \helps with acute infection, but a later response can cause bad things like tissue damage. Sounds bipolar. IL8 is an indicator of a damaging response. The MIG response, according to Rich, is a most accurate measure of the TH1 T Cell Helper response, and this would confirm the earlier gamma interferon positive result. This was described as very valuable to the FDA.
Things got crazy. Rich sat up. We now know that IL6 response was there. Rich said "this is great for us. It indicates that the CD4 T Cells are recognizing the peptides and therefor can generate a beneficial response." Nice. IL8 was elevated in all of the samples, especially in those only 3-4 weeks out from having covid, as compared to samples that were 3-4 months out. The Ii-Key vaccine properly did not induce further levels in IL8. That's good. There's no threat of cytokine storm. The MIG results confirmed the gamma interferon, rather worded as a good correlation. This indicated that the vaccine is skewing towards TH1, which is exactly what Generex wanted to see.
Generex wasn't done testing. And this is also important. Rich whispered how they completed an evaluation of HLA alleles. He noted that its similar to how doctors screen patients for transplant matches, something I've experienced by donating my kidney. I've read over the years about other peptides, like E75 or GP2, that didn't really cover a lot of the population due to HLA restrictions. Generex completed their evaluation and determined that their II-Key covid vaccine has broad coverage of greater than 95% across populations.
Joe texted Rich to calm down, but Rich kept pressing. Next, he said Generex also did an antibody binding test across serum samples at UCSD. The live assay showed that the Ii-Key epitopes did bind to antibody from the serum. This was a good surprise because antibodies mostly bind to 3D structures and not linear epitopes like Generex has. So, now Generex selected 5 Ii-key epitopes that bind to antibodies and which illicit the proper T Cell response. This is like having a starting line in place for an eventual Super Bowl champion team. Generex and their partners made a laboratory batch (which is in the immunogenicity study.
The immunogenicity study is of transgenic mice that have a piece of the human immune system called DR4. This is a HLA allele that will recognize the human specific epitopes of the Ii-Key vaccine. Rich was now rocking and rolling. He said "we vaccinated the animals with and without the 3M adjuvant. We vaccinated at different doses. We sacrificed the animals this week. The spleens were collected and shipped to CTL's lab in Ohio for the T Cell analysis and the serum was shipped yesterday." He then said was received and ten days or so we will know if we have a Complete Vaccine. He correctly explained that they know from their historical Ii-Key data, most notably the 10 year data for the AE37 BC vaccine, that the vaccine should activate the T Cell response necessary for long term immunity. They need to see that they generate the neutralizing antibody response.
As Rich exclaimed, they "waited until they had the science first. We let the science drive our decisions all along. And by doing that we have a lot of information about the immunologic regulation of our vaccine prior to even going into human studies, because we've been working with ex vivo human samples, so we know we have human data."
Mic drop. Rich sent the call back to Joe.
I noticed he thanked a NGIO Advisory Board member named Thomas Rodgers. He thanked him for leading the antibody work done in the labs at UCSD. He has an impressive profile page at UCSD. I recall a recent article from Malaysia where Joe is quoted as saying a peer review for this work is authored by TF Rodgers. So here's our guy with the Ii-Key Covid/Sars peer review to soon be on this page:
https://profiles.ucsd.edu/thomas.rogers
Rich excited the listeners by enthusiastically noting Generex's partnership with EpiVax! He called them a partner in computational vaccinology that utilizes an algorithm to identify the best epitopes for a vaccine. Think of a dart board player that only throws bullseyes. So, out of thousands of epitopes found in the spike membrane proteins of the Corona virus, Generex and EpiVax selected 33 epitopes with the highest probability of being highly immunogenic. The team manufactured and tested those 33 at CTL "Cellular Technology Limited" (http://www.immunospot.com/about/about-immunospot) in Ohio.
Things got exciting as Rich mumbled about the T Cell Assay and Elispot Assay test for gamma interferon. This gamma interferon measures TH1, the good T Cell helper cells. The gang also measured for Enzyme B, which indicates the presense of CD8 killer cells. They tested for IL5 which indicated the trend towards TH2 the negative CD8 response that they don't want to see since that could bring around the potential for cytotoxic storm.
The suspense was building. Rich explained that Generex tested 46 blood samples for human patients that had covid. They tested 31 samples from patients that didn't have covid. Their samples were collected by Generex's partners in 2017/18. The goal was to see if the Ii-Key Covid vaccine was generating specific immune reactions against covid-19 rather than against normal human blood virus that may have been exposed to previous corona virus infections.
And we have our results. Joe needs to give Rich a Red Bull. Anyway, the results of the T Cell Assay show a positive reaction for CD4 TH1 response with gamma interferon. They show a positive response for CD8 killer T Cell. They show no indication at all with TH2 response from IL5 (pronounced aisle 5 like at WalMart.) That was the response hoped for across the board. As Rich stated, "we are very excited, the results are very encouraging." He sounded it! But seriously, this very good news.
These are the assay results we needed. They are completely positive. Evidently, TF Rodgers is writing the peer review.
The fun isn't over. Rich informed that the FDA requested a Immunogenicity study. Tension was in the air as he explained that a cytometric bead array to measure other cytokines measured by IL6, IL8 and CXCL9/MIG. Common topics people talk about every day. Rich explained that IL6 had good and bad effects that either early on \helps with acute infection, but a later response can cause bad things like tissue damage. Sounds bipolar. IL8 is an indicator of a damaging response. The MIG response, according to Rich, is a most accurate measure of the TH1 T Cell Helper response, and this would confirm the earlier gamma interferon positive result. This was described as very valuable to the FDA.
Things got crazy. Rich sat up. We now know that IL6 response was there. Rich said "this is great for us. It indicates that the CD4 T Cells are recognizing the peptides and therefor can generate a beneficial response." Nice. IL8 was elevated in all of the samples, especially in those only 3-4 weeks out from having covid, as compared to samples that were 3-4 months out. The Ii-Key vaccine properly did not induce further levels in IL8. That's good. There's no threat of cytokine storm. The MIG results confirmed the gamma interferon, rather worded as a good correlation. This indicated that the vaccine is skewing towards TH1, which is exactly what Generex wanted to see.
Generex wasn't done testing. And this is also important. Rich whispered how they completed an evaluation of HLA alleles. He noted that its similar to how doctors screen patients for transplant matches, something I've experienced by donating my kidney. I've read over the years about other peptides, like E75 or GP2, that didn't really cover a lot of the population due to HLA restrictions. Generex completed their evaluation and determined that their II-Key covid vaccine has broad coverage of greater than 95% across populations.
Joe texted Rich to calm down, but Rich kept pressing. Next, he said Generex also did an antibody binding test across serum samples at UCSD. The live assay showed that the Ii-Key epitopes did bind to antibody from the serum. This was a good surprise because antibodies mostly bind to 3D structures and not linear epitopes like Generex has. So, now Generex selected 5 Ii-key epitopes that bind to antibodies and which illicit the proper T Cell response. This is like having a starting line in place for an eventual Super Bowl champion team. Generex and their partners made a laboratory batch (which is in the immunogenicity study.
The immunogenicity study is of transgenic mice that have a piece of the human immune system called DR4. This is a HLA allele that will recognize the human specific epitopes of the Ii-Key vaccine. Rich was now rocking and rolling. He said "we vaccinated the animals with and without the 3M adjuvant. We vaccinated at different doses. We sacrificed the animals this week. The spleens were collected and shipped to CTL's lab in Ohio for the T Cell analysis and the serum was shipped yesterday." He then said was received and ten days or so we will know if we have a Complete Vaccine. He correctly explained that they know from their historical Ii-Key data, most notably the 10 year data for the AE37 BC vaccine, that the vaccine should activate the T Cell response necessary for long term immunity. They need to see that they generate the neutralizing antibody response.
As Rich exclaimed, they "waited until they had the science first. We let the science drive our decisions all along. And by doing that we have a lot of information about the immunologic regulation of our vaccine prior to even going into human studies, because we've been working with ex vivo human samples, so we know we have human data."
Mic drop. Rich sent the call back to Joe.
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