Mccareer.files.wordpress.com



Proposal: Low Cost and No Risk COVID-19 Vaccine BoostersPlease read the 700-word outline below. It presents a no risk, no delay, very inexpensive research plan to reduce the cost and improve the speed of worldwide distribution of the coming COVID-19 vaccines. If it makes sense to you, please pass it on to anyone you know who might be able to make it happen. Kenneth Frumkin, PhD, MD1121 N. Bethlehem Pike Ste 60-136Spring House PA 19477(757)482-9384; FAX: (757)482-9386Kenneth.Frumkin@in/KennethFrumkinPhDMDConditioning the Immune Response to the COVID-19 Vaccine - No Delay, No Risk, Low Cost:Brief Literature Review and Proposed Research DesignIn Pavlovian conditioning, learned associations are made by pairing a novel inactive conditioned stimulus (CS) and an active agent (a drug, chemical, or environmental means that produces a physiologic effect), the unconditioned stimulus (US). After pairings, the neutral CS alone comes to elicit a response characteristic of the active (unconditioned) agent. The relevant initial demonstrations of the strength and reproducibility of such conditioning began by pairing poisons with novel tastes in rats. After pairing, the neutral stimulus (CS) alone comes to elicit a response characteristic of the agent. Those animals that survive the poison subsequently avoid the taste stimulus, a “conditioned taste aversion”.1 A very powerful form of conditioning, such associations can be learned within just one trial, conferring obvious substantial evolutionary advantages. Subsequent research demonstrated that the same conditioning paradigm (pairing a unique taste and a biologically active agent) could successfully condition both suppression and enhancement of the immune system.2, 3 Examples of learned immunosuppression using chemotherapy agents in humans include conditioned suppression of the T-cell response, general leukopenia, and other measures of immune function. 4-6 Learned immunoenhancement of the response to a vaccine occurs when a neutral stimulus previously paired with the antigen is subsequently administered alone. Like a vaccine “booster” the conditioned stimulus enhances antibody production7-11, learning that can occur in just one trial 9, 12Proposed Research:Antibody Response to A Benign Conditioned Stimulus Previously Paired with Administration of COVID-19 Vaccine.The supporting animal research goes back decades and is solid. Human studies are uncommon but demonstrate the efficacy of conditioned stimuli in substituting for active drugs to reduce doses and side effects.13, 14 The lack of incentives for the pharmaceutical industry to pursue such work is obvious: a safe and inexpensive conditioned substitute for repeat vaccine doses would preclude repeat sales. As a likely consequence, most studies have been done outside the US, and are small.The simple, safe study can be piggybacked with minimal interference onto one or more of the coming Phase II and III trials examining the humoral immune response to new corona vaccines. Creating an experimental group given a unique taste stimulus (think of an oddly flavored jelly candy or fruit drink) at the time of vaccine administration will add no risk and minimal extra effort. A successful demonstration would make the benefits of a very cheap corona vaccine booster dose available on-demand, worldwide, at a cost of pennies. Experimental design: (1)Administer the conditioned stimulus (CS), a unique taste, to half those receiving the first vaccine dose (Experimental Group). (2)Measure antibody levels in all, as would normally be done in the Phase II or III protocol. (3)At the time of the second dose of the vaccine, give the CS again to the Experimental subjects, and the second vaccine dose to all. (4)Measure antibodies in all at an appropriate time after the second vaccine dose. (5)Then give just the CS again to the Experimental group. (6)Finally, measure antibody levels in all after the next study interval. Any difference in antibody levels between the groups at any time would be attributable to conditioning of the antibody response to the CS. Challenges/Benefits: There is a reasonable likelihood of success based on animal data, and no good scientific or economic reason not to do it: There is no added risk to participants, minimal change to standard vaccine development protocols, and a remarkable upside for a world in which one would ideally immunize everyone against COVID-19. If one “Gummy Bear?” or equivalent could substitute for a second vaccine dose in the standard regimen, or even for a 3rd or 4th “booster” in a resurgent pandemic, the ability to immunize the world’s population would be vastly improved. Unlike most challenges created by COVID-19, performing this study would have the unique expanded scientific benefit of answering the question: Can we employ conditioning in routine immunologic practice? Given the low cost, safety, limited complexity, the potential value of such a study, and the number of agencies and companies worldwide developing vaccines, one would hope someone could be interested. My recent broad review of this phenomenon (Journal of Emergency Medicine, in press, 2020) can be downloaded at ()REFERENCES1.Welzl H, D'Adamo P, Lipp HP. Conditioned taste aversion as a learning and memory paradigm. Behav Brain Res. 2001;125:205-213.2.Hadamitzky M, Sondermann W, Benson S, Schedlowski M. Placebo Effects in the Immune System. Int Rev Neurobiol. 2018;138:39-59.3.Niemi MB, Pacheco-Lopez G, Engler H, Riether C, Doenlen R, Schedlowski M. Neuro-Immune Associative Learning. In: Lajtha A, Galoyan A, Besedovsky HO, eds. Handbook of Neurochemistry and Molecular Neurobiology. Boston, MA: Springer; 2008.4.Goebel MU, Trebst AE, Steiner J, et al. Behavioral conditioning of immunosuppression is possible in humans. FASEB J. 2002;16:1869-1873.5.Giang DW, Goodman AD, Schiffer RB, et al. Conditioning of cyclophosphamide-induced leukopenia in humans. J Neuropsychiatry Clin Neurosci. 1996;8:194-201.6.Albring A, Wendt L, Benson S, et al. Preserving learned immunosuppressive placebo response: perspectives for clinical application. Clin Pharmacol Ther. 2014;96:247-255.7.Ader R, Kelly K, Moynihan JA, Grota LJ, Cohen N. Conditioned enhancement of antibody production using antigen as the unconditioned stimulus. Brain Behav Immun. 1993;7:334-343.8.Ader R. Conditioned immunomodulation: research needs and directions. Brain Behav Immun. 2003;17 Suppl 1:S51-57.9.Alvarez-Borda B, Ramirez-Amaya V, Perez-Montfort R, Bermudez-Rattoni F. Enhancement of antibody production by a learning paradigm. Neurobiol Learn Mem. 1995;64:103-105.10.Pacheco-Lopez G, Niemi MB, Engler H, Schedlowski M. Neuro-Immune Associative Learning. In: Bermudez-Rattoni F, ed. Neural Plasticity and Memory: From Genes to Brain Imaging. Boca Raton (FL): CRC Press; 2007.11.Vits S, Cesko E, Enck P, Hillen U, Schadendorf D, Schedlowski M. Behavioural conditioning as the mediator of placebo responses in the immune system. Philos Trans R Soc Lond B Biol Sci. 2011;366:1799-1807.12.Madden KS, Boehm GW, Lee SC, Grota LJ, Cohen N, Ader R. One-trial conditioning of the antibody response to hen egg lysozyme in rats. J Neuroimmunol. 2001;113:236-239.13.Vits S, Schedlowski M. Learned Placebo Effects in the Immune System. Zeitschrift fur Psychologie. 2014;222:148-153.14.Sandler AD, Glesne CE, Bodfish JW. Conditioned placebo dose reduction: a new treatment in attention-deficit hyperactivity disorder? J Dev Behav Pediatr. 2010;31:369-375. ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download