Learning from Dr. Fauci

Listening to Dr. Fauci’s portion of the Covid 19 response team briefing on March 5, 2021 on MS-NBC gives the wonderful experience of being taught by a world-class scientist. He suggested some homework, reading an article by John P Moore, PhD. (JAMA 2021 published March 4, 2021). I will attempt to summarize the key points Dr. Moore makes.
Dr. Moore notes that South African and Brazilian variants (B.1.351 and P.1, the antibody and possibly vaccine resistant variants) have “sequence changes in key positions suggesting that they arose under neutralizing antibody selection pressure within people infected or previously infected with SARS-CoV-2. Unusual variants have been seen when the virus replicates at high levels for prolonged periods in immunocompromised individuals.”
He goes on to state that while a strong neutralizing antibody response suppresses virus replication, and a weak response does little to suppress replication, “neutralizing antibodies of intermediate potency are thought to cause the virus to evolve and create ways to escape the constraint on its ability to replicate.”
The “combination of a high virus replication rate within an individual (a high viral load) and a suboptimal level of neutralizing antibodies is the exact environment in which resistant viruses are considered likely to emerge and spread.”
Ominously, the B.1.351 variant was found (in lab experiments) to be partially resistant to neutralizing antibodies induced by 2 doses of the Pfizer mRNA or the Moderna mRNA vaccine. (Implication: don’t feel free to do what you want after 2 doses)
In 2 reports, single dose Pfizer vaccine serum antibodies could not neutralize B.1.351 at all.
Vaccines are less effective during the period between the first and the second dose, and when people are infected in this interval, “the virus can replicate in the setting of a suboptimal of neutralizing antibodies, a situation in which resistant variants may emerge”.
This argues for a short period between the 2 doses of Pfizer or Moderna, which is not the policy in the UK, where a variant of B.1.1.7 (the original is more infectious but not vaccine resistant) containing the E484K substitution in the S (spike) protein has been detected. The E484K substitution is considered a hallmark of neutralizing antibody resistance.
The single-dose Johnson & Johnson vaccine raises the concern that resistant viruses will arise in J&J vaccine recipients if the efficacy of the single dose “wanes over time”. As for giving a 2nd dose of the J&J vaccine, there is a possibility that antivector immunity (to the adenovirus that carries the antigenic material) compromises the efficiency of a second, identical adenovirus dose. Unlike the J&J and the AstraZeneca, which use the same adenovirus vector for each injection, the Russian Sputnik V uses different adenovirus vectors for each injection, and reportedly has higher efficacy.
The concept of “original antigenic sin” is a scenario in which a redesigned vaccine (eg to go after the E484K sequence change) “boosts only the original neutralizing antibody rather than eliciting a new set of antibodies that are intended to target the new virus variant.” Experiments are needed to determine if this applies. If it applies, it would complicate making upgrades to the vaccines we have now.
Thank you, Dr. Fauci, for this learning experience.

This entry was posted in First Comments. Bookmark the permalink.

Comments are closed.