Vaccine Escape and Drug Resistance – No free lunch
Vaccinations are meant to provide an edge for at risk patients to help them fight off infections that they may otherwise succumb to. They don’t necessarily prevent infection all the time but the positive effects on reduced hospitalization and mortality are very apparent. Their use should be guided by the individual risk and benefits of therapy. This should be obvious; your grandmother is more in need of a flu or covid vaccine than you are, mostly to protect her from all the filthy things you bring over. This has been an accepted fact in medicine for a long time, vaccines for things like shingles and pneumonia are not even thought about unless the patient is over a certain age or immunocompromised. If you're old and overweight I will most certainly harp on getting a flu shot every year, if you're young and healthy I will encourage you to do so as well but when met with resistance my oxygen is best spent elsewhere.
Many fools heralded penicillin as the end of microbial infections since it was such a wonder drug. If only we had given penicillin to everyone in the world at the same time there would be no more bad bacteria left. Surely the greatest generation could have taken one for the team and had mandatory antibiotic therapy to slow the spread. Only two decades previously the horrors of World War I and trench warfare had failed to take as many American lives as the Swine Flu Pandemic of 1918. Yet this opportunity to once and for all stop the bacterial menace slipped away.
Replacing vaccination with penicillin in this story above allows its absurdity to come into full focus. Indeed prior to Covid antimicrobial stewardship was a big deal and the debate about over prescribing antibiotics was heated on both sides. Multidrug resistant organisms are now quite common, and penicillin has been pushed to the back of the shelf in favor of more modern and effective antibiotics which are slowly losing ground to emerging resistances. Giving antibiotic therapy to those that did not need it was almost universally frowned upon as a bad idea, so much so that telling you to go home and suck it up was as likely an outcome of a doctor visit as getting a prescription. In the age of Covid however antimicrobial stewardship be damned, Doxycycline and Azithromycin were prescribed like opiates in 2003 as a throw the entire kitchen sink at the virus attitude was adopted.
Like all policies the vaccine mandate comes from a place of good intentions, so we are told at least that’s the beauty of intentions they are always golden in appearance no matter how bad the smell. You must all be vaccinated of course so that you do not pass the infection onto others. The theory being that once we have all gotten the vaccine Covid will have nowhere to hide and disappear completely. Unfortunately, this idea is based on a foundation shakier than a Haiti high rise. There is no such thing as a free lunch, there is always push back in nature. Coronaviruses have always been with us causing a variety of our common colds and thanks to a boost from humans have now skipped a few centuries ahead on the evolutionary ladder.
You won’t find vaccine resistance in the literature very often because the term that is used to describe this situation is vaccine escape. As the virus has spread worldwide mutations and variants have flared up. The Delta variant has received the most attention, originating in India it is more transmissible and has shown to reduce the effectiveness of our current vaccines. A recent analysis of 506,768 genome isolates from positive Covid patients would identify a hundred mutations that have increased affinity for the ACE2 enzyme and the receptor binding complex compared to the initial alpha version. The researchers have hypothesized that further genetic evolution of the virus could compromise our existing vaccines and antibody therapies. My greatest fear is that our excessive use of these vaccines in a population that arguably may not need them could result in a reduced effectiveness for the population that does. I hope this proves to not be the case but expressing the idea should not be verboten.
This principle of stratifying therapeutics most effectively throughout the population has now reared its head in our public booster battle between the CDC, FDA, and the White House. The FDA advisory panel rejected the boosters for all plans that had already been announced by the administration, while giving the ok for the elderly and immunocompromised. Two long standing FDA doctors would retire in objection and take their complaints public with an opinion article in the Lancet. A few days later the CDC would expand the guidance a little further to include healthcare workers as well. Dr. Fauci would take to Sunday morning talk shows to promise new future science and data that would take us back to the boosters for all. All of this has created a quagmire of public confusion, resentment and animosity towards one another over personal healthcare decisions that due to patient privacy laws none of us even have a right to know about.
Jacob Hyatt, Pharm D.
Father of three, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
https://substack.com/discover/pharmacoconuts
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Further Reading and References
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02046-8/fulltext
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(17)30489-5/fulltext
Dyar OJ, Huttner B, Schouten J, Pulcini C; ESGAP (ESCMID Study Group for Antimicrobial stewardshiP). What is antimicrobial stewardship? Clin Microbiol Infect. 2017 Nov;23(11):793-798. doi: 10.1016/j.cmi.2017.08.026. Epub 2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190532/
Huttner BD, Catho G, Pano-Pardo JR, Pulcini C, Schouten J. COVID-19: don't neglect antimicrobial stewardship principles!. Clin Microbiol Infect. 2020;26(7):808-810. doi:10.1016/j.cmi.2020.04.024
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029448/
Nel AE, Miller JF. Nano-Enabled COVID-19 Vaccines: Meeting the Challenges of Durable Antibody Plus Cellular Immunity and Immune Escape. ACS Nano. 2021;15(4):5793-5818. doi:10.1021/acsnano.1c01845
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123493/
Wang R, Chen J, Gao K, Wei GW. Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries. Genomics. 2021;113(4):2158-2170. doi:10.1016/j.ygeno.2021.05.006
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402596/
Saso A, Kampmann B, Roetynck S. Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines. Vaccines (Basel). 2021;9(8):877. Published 2021 Aug 7. doi:10.3390/vaccines9080877
https://www.nature.com/articles/d41586-021-01696-3
Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 2021 Jul;595(7865):17-18. doi: 10.1038/d41586-021-01696-3. PMID: 34158664.
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723407/
Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020;9:e61312. Published 2020 Oct 28. doi:10.7554/eLife.61312
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/
Greaney AJ, Starr TN, Gilchuk P, et al. Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition. Cell Host Microbe. 2021;29(1):44-57.e9. doi:10.1016/j.chom.2020.11.007
