When your immune system is first stimulated by an antigen (the invader), a bunch of different B cell clones will produce a specific antibody that targets the antigen. In final selection, there is a whole group of B cell clones that can bind to different regions of the antigen. This is called a polyclonal B cell response. The antibodies from each clone bind to different parts of the antigen. This diversity ensures robust neutralization of the antigen.
When there is a second stimulus by the same antigen, there may still be neutralizing antibodies present depending on how long they remain in circulation. Memory B cells from the first stimulus can also make more antibodies. These act faster and have higher levels than the primary immune response. However, you can still activate brand new B cells and create yet another set of antibodies, all with their own slightly different structure. That increase in diversity could increase your chances of having antibodies that can successfully neutralize the Delta variant.
A third stimulus will do the same thing, although at some point you will no longer see a benefit. However, Pfizer’s data is showing stronger neutralization activity after a third shot for both WT and Delta (slide 27). That should cut down on breakthrough infections.
We also don’t know if the diversity you’re talking about is particularly important in the case of covid. There might be one or two great binding sites and we don’t need an infinite variety.
And while I appreciate what you put together there, do you have an immunologist or someone who is agreeing with your take? Because I sense, like me, you are self taught and this is a subject where some sound knowledge can still lead to very wrong conclusions because we missed something.
At the end though personally, triple vaccination to stop breakthrough infections doesn’t sound like the best use of current vaccine supplies.
I hadn’t really heard anything like that. Firstly, the vaccines don’t have any binding site, they are intended to evade the immune system and get into cells. What you probably meant was the protein they cause the cells to make has only one binding point? AIUI they produce a spike protein and the immune system picks the binding sites. You could make a vaccine like that, I assume, but that’s not what I understand to be the case.
I thought they went to production with the “subunit” vaccine rather than the “Whole Protein” vaccine. I was probably wrong. Does anybody here have the citation/ vaccine identifier?
My PhD was in biochemistry and molecular biology and published research was not in immunology, so I’m not an expert in that field and certainly not up on the current literature. However, in my semi-retirement, I have taught nursing microbiology (which includes immunology) so I’m a familiar enough with the adaptive immune system to have some idea of what Pfizer is trying to do.
By the way, your link is describes the nucleocapsid protein. This is a completely different region of the virus. People with more advanced Covid and poor prognosis tend to have higher anti-N antibodies. They’re not sure why but they postulate that the the anti-N antibodies produce a more dangerous inflammatory response or they simply are diagnostic of morbidity because N proteins are only released after cells are infected (and probably dead). It’s better to design a vaccine against the entry protein (spike protein). It seems like the authors in your science news article are interested in using the N protein as a target for small molecule therapeutics. Those could penetrate the viral envelope, bind to the N protein and disrupt the virus. That’s doable.
Well, I certainly bow to your superior knowledge. It’s just that I don’t see anyone getting quoted backing up Pfizer the way you are and it’s a decently big covid story. Is there anything in more professional newsites/journals?
Yes. The BNT162b1 vaccine is a trimer of the receptor binding domain of the spike protein. It’s the part of the spike protein that pokes out in the figure to bind to the ACE2 receptor.
Obviously they are planning to publish this as was stated in the article and the slides from their conference. It’s brand new information. I don’t need to quote someone when I’m discussing how the adaptive immune system works unless you want me to link you to some textbooks. The idea that more than one challenge to the immune system increases immunity is not a novel idea. And, yes, you’re right that there probably is a threshold where you’d no longer see an improvement in immunity. Pfizer’s data demonstrates that that threshold has not yet been reached. Of course, those are neutralization studies in vitro, but they’re promising, unless you think they’re making it up.
Well, I think it was a study of 23 people. I believe the current consensus that the vaccines give pretty solid protection past 6 months. I figure profit is why they are not the most objective judges of the results. But no I certainly don’t think they’re lying.
It’s been under the radar for awhile (at least my radar), but the Novavax vaccine is looking great. I was recently reading a report arguing for investing in NVAX stock. Unfortunately, the report is paywalled, and I can’t link to it. The thesis is that the Novavax vaccine -
has the highest efficacy when compared on a like-for-like basis (Novavax trials also include variants, against which it maintains high efficacy)
has the same or lower side effects as current vaccines in use
has lower production costs
has no need for expensive refrigeration (=lower logistics costs)
is expected to receive US and EU authorization in Q3 2021
uses more traditional methods of vaccine production
Obviously the first bullet point is very encouraging, but the last is perhaps even more important. There are people hesitant to take the mRNA vaccines due to their experimental nature. The underlying science of Novavax’s vaccine has been known for decades. Science Magazine said the following:
To make their vaccine, Novavax scientists first used a baculovirus to insert the gene for the SARS-CoV-2 spike protein into moth cells, which produced the spikes on their cell membranes. Scientists then harvested the spike proteins and mixed them with a synthetic soaplike particle in which the spikes embed. A compound derived from trees serves as an immune-boosting adjuvant.
This is the same technology used to produce Hepatitis B vaccines since 1986 as well as the pertussis vaccine which is mandated for all children in the US. I hope that some people hesitant to take the mRNA vaccines might find Novavax more appealing.