By Rud Istvan
Since respected ‘experts’ like Dr. Fauci are saying there is no return to normal until an effective vaccine is widely available, I thought I would use my hard earned infectious disease knowledge, (previously explained in Wuhan post #1) plus a day of new research to provide a WUWT synopsis of at least a present partial state of play, deep diving on two of the US most promising vaccine candidates. (There are at least 8 promising vaccines in active global development; too many to globally cover in detail in this guest post.)
The true origin was from Dr. Jenner in 1796, when he observed that a mild cowpox infection protected from deadly smallpox infection, and then tested that observational hypothesis on 8 year old James Phipps before his (now ethically unthinkable) variolation. See www.ncbi.nlm.nih.gov/PMC1200696 for the details of this miracle. Older American smallpox vaccination shoulder scars are merely the scratched sites of your single mild cowpox infection vaccination, no different than young James Phipps in May 1796.
The general vaccination idea is to alert the immune system (both B cell humoral antibodies and T cell killer systems, if possible) to pathogen antigens without triggering the actual disease. If the disease pathogen does later arrive, the immune system is “primed” to defeat it rapidly. Many deadly diseases have been mostly defeated thanks to vaccination, including smallpox, polio, pertussis, measles, mumps, rubella (MMR), …
The antivaxxer canard that MMR vaccine causes autism goes back to a very small sample scientific scandal by a crooked British gastroenterologist, explained in detail in the Coincidence chapter of my ebook The Arts of Truth. Short medical synopsis: the digestive tract has little to do with brain function. Short coincidence synopsis: autism does not manifest before 18 months of age, and only sometimes thereafter; until then the brain is still ‘sculpting’ connection/removal of neurons. (A blind ‘lazy eye’ is one physical example of this early neuron sculpting process.) It so happens that pediatricians recommend MMR vaccination at around 18 months to 24 months, when autism can first manifest.
There are at least two insurmountable potential Wuhan vaccine problems.
- Some vaccinations last for a lifetime (smallpox). Others do not (chickenpox/shingles partial lifetime, tetanus ~5 years). We dunno what might be the case for Wuhan.
- Viruses, especially RNA viruses (see rumination #1) mutate. That is why the annual flu vaccine ranges from good to bad. The vaccine targets three or four of the most commonly circulating flu varieties from this year, for next year’s vaccine. The problem is that the virus is always mutating, so by the end of next year what is circulating is mostly mutations of the types last year’s vaccine missed. We do not know yet the rate of Wuhan mutation. It appears maybe less that influenza, but we already know of at least 40 mutations, plus a less virulent US West Coast strain directly from China, and a more virulent East Coast strain imported from China via Italy. (Why Gov. Cuomo said NY had a European virus problem.) So how good the coverage of a possible Wuhan vaccine might be is also a speculation.
It is an enveloped single stranded positive sense RNA virus. It has three neutralizing antibody targets: capsid N protein, and the S1 and S2 sites on the S spike protein. See rumination #6. With careful antibody selection, these can provide exquisitely good antibody test/vaccine targets. The newly EUA approved Abbott antibody test is 99.6% sensitive and 100% specific! (See rumination #6 for the HUGE beneficial significance of this new Abbott antibody test development compared to the Becton-Dickenson test announced a month ago.)
But except for a canine enteric coronavirus vaccine (Merck Animal Health), which does NOT protect against the canine respiratory form of the same virus, there has NEVER been a successful coronavirus vaccine developed–ever. So despite Dr. Fauci’s hopes and efforts, that may well remain true with Wuhan. This is a risky uncharted business with significant economic consequences.
There are in the US at least two interesting and very different initiatives. What makes them scientifically interesting is that they both come from new science ‘vaccine platforms’. That is, a more general purpose scientific/laboratory system that pre-existed Wuhan, enabling faster specific vaccine development.
The fastest, and IMO riskiest, platform is Moderna Therapeutics, who have finished Phase 1 and just got FDA EUA permission to go into Phase 2 testing in humans. (For the uneducated about formal FDA stuff required by the statutory PFDA Act of 1906 as later amended–and renamed the FDCA–EUA means Emergency Use Authorization (cutting regulatory corners), Phase 1 is a few tens of humans primarily for safety, Phase 2 (which can have A dose ranging and then B efficacy subparts) in more humans (hundreds), and then Phase 3 where the P2A/B selected dose is tested for safety and efficacy in many (thousands), which if it works and is safe eventually leads to FDA legal approval).
The Moderna platform was conceived only for viruses. In this case, it is using synthetic messenger RNA (mRNA) from Wuhan, hoping that the immune system will respond to the injection of those foreign nucleoside entities with neutralizing antibodies. They were fast because they already had the RNA platform, so as soon as Moderna got the Wuhan RNA genetic code late January, they could identify likely antibody targets.
Unfortunately, the just passed Phase 1 safety trial COULD mean it simply doesn’t work at all. Moderna has never gotten a vaccine approved off its platform despite being founded in 2010. Maybe this time will be different. Whether if successful they can scale production is unknown—the CEO just said that if approved, its vaccine would be limited in quantity.
The other big US platform is J&J’s Janssen Pharmaceuticals. Their platform has also been developing for several years, and has two components. They have a genetically modified human common cold adenovirus (AdVir) that is used as a vaccine genetic carrier. The adenovirus modifications mean it CANNOT anymore replicate in humans; it just delivers DNA. (Remember from my post 1, adeno is only 5% of common colds, but is a DNA virus.) Plus, a human derived special (epithelial?) cell line where the modified adenovirus can rapidly replicate in large (1000 liter) bioreactors to make lots of vaccine ‘virus’ carrier” fast despite not in humans. They have used this platform to develop potential vaccines for Zika, RSV, and HIV, all in Phase 2-3 testing. So a lot of the background human FDA sciency/safety viral carrier stuff has already been done.
They used this platform to insert a variety of Wuhan potential RNA (transcribed as DNA) immune system targets into AdVir in late January (the transcribed DNA replication versions of the RNA viral messenger protein(s) fragments, hopefully), then used animal testing to select a primary vaccine candidate plus two backups for further “transcribed DNA’ animal testing now ongoing. They hope to be in humans (skipping platform unnecessary Phase 1 safety) in September, and say they could be producing millions of doses monthly by early 2021. This, IMO, has a good chance of succeeding given both the platform and the process they are using, despite the fact that it is a DNA, not RNA, genetic viral system. Maybe our immune systems do not care in which form the viral genetics are presented. We can hope.
This is complicated stuff. We are seeing some of the best of modern science (genetic sequencing, Moderna, J&J) and some of the worst (Neil Fergusons’s Imperial College epidemiological model garbage coding) on display at the same time. As said before, analogies to ‘climate science’ are legion. As a simple coding example, naive infectious rate R0 is both an input and an output in all epidemiological models depending on personal behaviors. (Naives, self-distancings). BIG math model PROBLEMs unsolvable except by beliefs