Source: rwmalonemd.substack.com
As previously covered (here), the currently available FDA emergency use authorized “booster vaccines” were designed based on recommendations developed at the FDA VRPBAC (vaccine and related products biological advisory committee), which predicted that the dominant SARS-CoV-2 variant this fall would be the “Kraken” (XBB.1.5) viral variant of Omicron.
To re-cap, the FDA and it’s advisory committee are operating based on the hypothesis that the dominant mechanism of protection against SARS-CoV-2 infection, spread, and COVID-19 disease afforded by vaccination or natural immunity involves “neutralizing antibodies”. This hypothesis is unproven, and no immunologic “correlate of protection” which predicts protection from either infection or disease has been clinically proven. To the extent that high levels of human “neutralizing antibodies” from the SARS-CoV-2 genetic “vaccines” provide any protection, they seem to “correlate” to reduced disease severity for some period after dosing, but do not prevent infection, replication, spread, disease or death.
Despite this undeniable fact, the FDA has disregarded its decades long policies concerning the requirement to validate a “correlate of protection” test before it can be used as a surrogate for actual clinical demonstration that a “vaccine” product will protect against infection, replication, spread, disease or death. Until so proven, historically a vaccine developer has been forbidden from making any claim of protection unless that claim is demonstrated and statistically ”validated”. Validation requiring some sort of well controlled human clinical trials. Alternatively, a vaccine developer can create a well-controlled “correlate of protection” laboratory test that employs human samples, and statistically demonstrate that it predicts (correlates) a relevant clinical outcome (ergo preventing infection, spread, severe disease of death). Only then can such the outcomes of such a test be used as a surrogate endpoint in clinical trials, rather than actually clinically testing whether the product has a significant impact on the intended endpoint.
Influenza vaccine development provides an example of this. In the case of influenza, a laboratory test called the hemagglutination-inhibition (HAI) test measures solutions of antibodies from patients that have a particular characteristic (laboratory clumping of red blood cells). With standard injected influenza vaccines, it has been statistically demonstrated that when a new vaccine is sufficiently potent at generating high enough levels of HAI antibodies (referred to as antibody “titer”), it will protect (to a significant degree) from clinical influenza disease. The nasal spray influenza vaccine (Flumist) did not meet the HAI lab test criteria, and so the developers at MedImmune were required to perform time consuming, expensive actual clinical trials to demonstrate that it protected against clinical disease. That was the way things used to be at the FDA, up until 2021 and the COVIDcrisis.
The process of statistical “validation” of a surrogate “correlate of protection” is rigorous, technically challenging, expensive, and time consuming. In the case of SARS-CoV-2, the CDC and FDA have arbitrarily decided to throw away normal regulatory standards and allow the substitution of non-validated assays as being predictive of efficacy or effectiveness of the COVID vaccines. Instead of taking the time to develop and statistically validate a test, they have relied on the multiple studies indicating that human “neutralizing antibody” levels are loosely associated with reduced disease severity, none of which have met criteria for statistical validation of that endpoint. All of these studies have used blood samples and lab test “titer” results averaged across many (human) patients, and the FDA now considers unvalidated “neutralizing antibody” tests to be generally correlated with short term protection against disease severity. The arbitrary and capricious use of such non-validated laboratory assays as a substitute for actual clinical trials proving that these products will perform as advertised has apparently been justified on the basis of expediency – the virus is evolving too fast to allow manufacturing and rigorous testing of these products before they are made obsolete by new viral variants.
Just to re-cap, the whole rationale for using Emergency Use Authorization to jam the modified-mRNA vaccine technology past the normal regulatory processes designed over decades to ensure safety and effectiveness was so that these products could be produced so rapidly that Pharma could promptly field effective vaccine products to protect the public from new viruses. Clearly, the technology and the EUA process bypass have failed to meet mission requirements for anti-viral effectiveness. And just as clearly the regulators have also thrown caution about vaccine product safety and adulteration to the wind. It is long past time to acknowledge that the most massive human experiment in the history of the world has failed.
The CDC Morbidity and Mortality Weekly Report (MMWR), a non-peer reviewed internal “official” publication of the CDC, has published a review article summarizing the data justifying the use of neutralizing antibody lab tests as a surrogate for clinical trials designed to actually prove vaccine protection, titled “Correlates of Protection, Thresholds of Protection, and Immunobridging among Persons with SARS-CoV-2 Infection”. The research reviewed focuses on the use of human sample testing, and includes the following conclusions:
The work on the vaccine-comparison model approach has so far shown that this model, which was originally calibrated on data for ancestral SARS-CoV-2 infections, can also be used to predict vaccine effectiveness against SARS-CoV-2 variants and after boosting, as long as one adjusts for the drop in neutralization titers to the variants and rise in neutralization after boosting (12,18,19; D. Cromer et al., unpub. data). However, the need to standardize neutralization assays for SARS-CoV-2 variants presents an ongoing challenge.
In vitro neutralizing antibody titers against SARS-CoV-2 present a clear correlate of protection from symptomatic SARS-CoV-2 infection. Studies of passive administration of neutralizing monoclonal antibodies in animals and humans support that neutralizing antibody titers are a mechanistic correlate of protection (21–23). Indeed, a recent study comparing protective titers in prophylactic and therapeutic studies suggests that the protective titers may be very similar (E. Stadler et al., unpub. data, https://www.medrxiv.org/content/10.1101/2022.03.21.22272672v2External Link). Neutralizing antibody levels are also correlated with protection from severe SARS-CoV-2 infection (2).
In conclusion, our findings show that the different COVID-19 correlate of protection studies, which seemingly report different thresholds of protection, have strong agreement. However, other immune responses may also play a substantial role in protection against progression from symptomatic to severe SARS-CoV-2 infection.
When you cut through the obfuscation, what the CDC authors are saying is that there does not appear to be agreement across the various publications concerning what levels of “neutralizing antibodies” are protective, but if you apply a statistical adjustment method, they can make the studies agree with each other. Which is probably why this is published in the CDC’s in-house, non-peer reviewed journal MMWR.
The publication basically asserts that an established viral neutralization assay can be useful in comparing the protection from disease or severe disease associated with different vaccine products (using human blood samples and statistical adjustments). However, as the virus evolves to new variants it becomes difficult to predict effectiveness of “vaccines” against these new variants. Furthermore, the publication indicates that predictive correlation of neutralization with infection (as opposed to disease) is much more problematic, and acknowledges that other immune responses (such as those elicited by natural infection) are likely to also play “a substantial role” in protection from disease progression.
So where does this leave the FDA and CDC in their efforts to justify Emergency Use Authorization of these products (disregarding the inconvenient fact that there is no emergency)? In the case of the currently available “booster” products, emergency use authorization was granted based on a “neutralizing antibody” titer test using blood (serum) from a small number of inoculated mice. Despite the exclusive reliance on human samples for this and virtually all other peer reviewed publications addressing the (unvalidated) correlation between “neutralizing antibody titers” and reduction in COVID-19 disease severity? How dosing equivalence between mice and man was actually determined was not shared with the likes of you and I. And I can assure you that is a very problematic calculation. Let alone whether said mice had been previously injected with prior versions of the vaccine. And overlooking how a hundred or more other immunologic variables which differentiate mice and man were (not) controlled for. One is left wondering if anyone in the decision making loop at FDA and CDC has any experience at all in immunology and vaccine research.
You see, the FDA and CDC had a problem. They were clearly told by their bureaucratic masters to get these “boosters” approved for the fall, but (as noted in the graphic above) they were designed to protect against the fearsome Kraken variant, but by the time they were ready for being jammed through EUA approval the Kraken (XBB.1.5) had become extinct, out competed by Eris (EG.5).
And as can be seen from the above phylogeny diagram, these two are on separate branches of the XBB tree. So what’s a regulator to do? Simple: rely on making vague, unsupported statements based on mouse serum cross neutralization assays, to the effect that the cross reactivity looks good enough to you. And know that since you are the expert (per Chevron deference), you can never be held accountable in the courts for your actions. And for extra protection against having your sloppiness and misdeeds detected, do not bother to allow anyone else to review the data. And make sure to activate CDC, DHS, and CISA tools and contractors to censor and defame anyone who has a different opinion. After all, the FDA and CDC authorities have had a perfect record of predicting what strategies and products will and will not work for preventing and treating COVID-19. Because, as was clearly stated in the Netflix 2023 remake version of the “Treasure of the Sierra Madre”, the FDA don’ need no stinkin’ data.
Please keep in mind that most of the rest of the word is done with this merry go round of booster de jour, but here in the good old USA, the FDA and CDC (and DHS, and CIA, and DoD) somehow think that the declining market capitalization of Pfizer and Moderna represent an existential threat to both public health and the US Biopharmaceutical-defense complex, and so we need COVID boosters forever….