More questions beyond the hype, hysteria, hesitancy and hostility: the greatest human trial ever (and the natural history of mRNA vaccine use) we had…

Dear Editors

Andy Extances essay provides interesting fodder for thought but what is not discussed is the hysteria (initially over the availability for use then over the potential side effects), (vaccine) hesitancy (predominately over the relatively new technology which has never been used in large population) and hostility (as a result of the divide between those who are vaccinated and those who are not, and in response to government mandate for compulsory vaccination in gazetted workplace and occupation) during this COVID-19 pandemic.

Perhaps the article attempts to focus on scientific aspects of mRNA vaccine development but I would suggest the ink is still not dry yet when considering claims of success of mRNA vaccine based on experience of Pfizer BioNTech (PBNT) and Modernas COVID-19 products.

Of interest, Andy Extance is right to flag the results of Modernas previous foray into mRNA vaccine experience, (ref 1) whereby the 2015 trials of flu mRNA vaccine showed that immunity was short lived.

Remarkably I dont recall any discussion of the longevity of the immunity induced by mRNA vaccine when PBNT was approved for emergency use in the last days of 2020, nor even within the first 6 months of its rollout in the US, UK and EU; perhaps I move amongst the wrong crowd but the first hint of the limits of mRNA immunity in my consciousness only came when the CEO of Pfizer suggested publicly that booster shots may be needed after 6-12 months of the initial shots (ref 2); this is when the US was still trying to get the majority of the population vaccinated, and before reports of increased infection in vaccinated individuals in Israel 6 months after double vaccination (ref 3)

At the time this was attributed to the emerging dominance of the highly infectious delta variant, although it was later found that the vaccines are only slightly less effective to Delta variant compared to the original Alpha type (ref 4).

Hence it was not due to emergence of Delta variant after all (even though this was still being peddled in mainstream media)

Looking at the previous Modernas study in 2015 (published in 2019), this waning immunity 6 months after double vaccination could have been predicted, but was not flagged for some time.

Another important question should be raised regarding mRNA vaccines:The marketing department flogging the advantages of mRNA vaccines suggest the technology made it easy to tweak the mRNA genetic material to address evolving variants of COVID-19 and yet there does not appear to be any new trial to test new subtype of mRNA vaccine to address the apparently new delta variant which was behaving distinctly differently in transmissibility compared to preceding types. Granted the clinical research based on epidemiological data proved the original PBNT was almost just as effective (ref 4) but this data is only available after 5 months worth of data (and status quo in vaccine production).

Was it clinical inertia and more profitable to simply keep producing the same product in the hope that it was just as effective in the meantime? Was it not worthwhile to start testing and making new subtypes of the mRNA vaccine specifically for the delta variant? Were the clauses and restrictions with emergency authorisation for use by the FDA, EMA and MHRA make it too troublesome to have to resubmit new trial data to allow extension to new subtype of mRNA vaccines previously approved under different circumstances (and virus type).

And I havent even commented on the quality issues and stability of mRNA vaccine against COVID-19 and related cold chain logistic issues which is still unresolved.

How about the curious matter of how BioNTech managed to get to the first vaccine to be approved for use in many parts of the world, despite the apparent vast experience of Moderna in mRNA vaccine development prior 2020?

Albeit the fact the PBNT only beat Moderna by just 7 days for emergency use by FDA, there is no doubt that the dominant mRNA vaccine outside the US is PBNT. Granted Pfizer has a far bigger manufacturing capacity than Moderna, setting up a factory to produce mRNA vaccines is not a feat that can happen with a few months.

So many questions that would intrigue historians of the future, some of whom are now eligible for vaccination (ref 7).

Reference1. Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine2019;37:3326-34. doi:10.1016/j.vaccine.2019.04.074 pmid:310798492. https://www.abc.net.au/news/2021-04-16/pfizer-boss-says-third-covid-vacc...3. https://www.abc.net.au/news/health/2021-09-09/covid-19-israel-vaccinatio...4. https://www.nejm.org/doi/full/10.1056/nejmoa21088915. https://www.nejm.org/doi/full/10.1056/NEJMoa21142286. https://www.abc.net.au/news/2021-11-26/new-covid-variant-in-south-africa....7. https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfize...

Read more:
More questions beyond the hype, hysteria, hesitancy and hostility: the greatest human trial ever (and the natural history of mRNA vaccine use) we had...