A 5th jab? Implications for the immune system

FDA advisory member hints at 'original antigenic sin'

Following the recent authorisation of the new omicron boosters, the former US Surgeon General encouraged Americans to receive two to four mRNA jabs annually.

Residents in northeast Australia have been told they might need a fifth dose by the end of the year.

In fact, it wasn’t that long ago that New South Wales’ top doctor said that people should expect to receive covid-19 booster shots “indefinitely.”

But could repeated covid-19 boosters at close intervals be causing more harm than good?  I speak with experts concerned that policymakers are not following the science.

Europe sounded the alarm

Earlier this year, the European drug regulator sent a dire warning to the world.  The agency was concerned that repeated boosters every four months could weaken a person’s immune response to the coronavirus.

Marco Cavaleri, the agency’s head of vaccines strategy, said that regular boosters might be “overloading people's immune systems and leading to fatigue.”

I spoke with Cody Meissner, an FDA advisory member, ahead of the agency’s April 6 meeting, during which experts were to discuss the evidence for a fourth dose.  He told me that he was not convinced by the data at the time. 

Prof Cody Meissner, FDA advisory member

“I personally don't think that we have sufficient basis on which to recommend a fourth dose, and we don't know what the harm will be,” said Meissner.

“The reason we're giving the vaccine is to keep people out of the intensive care unit and to keep people from dying, or even going into the hospital. So, before we vigorously endorse a fourth dose of this vaccine, I think we have to understand not only more about the immune response, but also about how much severe disease is occurring after three doses,” he added.

Meissner blamed socio-political interference for many of the questionable covid-19 strategies. “I think that the politicians and certain groups within society, such as the teacher’s union here in the United States, have driven a political agenda that is certainly not based on science. People like to say it's based on science. It's not. It's based on emotion and generating great fear,” said Meissner.

Despite the concerns, most policymakers have forged ahead with recommending third, fourth and fifth doses for large swathes of the populations.

But over the past year, observational data have emerged from countries like the UK, Scotland and Australia showing that the most highly vaccinated people are acquiring the highest rates of covid-19 infections, suggesting that the vaccines have lost their effectiveness or something unexplained is happening.

Multiple jabs, multiple infections

Meissner hinted at a possible explanation for why someone’s immune response could be suppressed after multiple covid-19 shots. “It gets into this issue of ‘original antigenic sin’, which is still a theoretical issue, but may have some validity it seems to me,” said Meissner earlier this year.

Original antigenic sin – scientifically referred to as immune imprinting – is a phenomenon whereby prior exposure to one virus strain (e.g. wuhan stain) limits the development of immunity against new variants (omicron strain), because the immune system has been “imprinted” to favour the original strain.

This leaves the immune system trapped because the antibodies it prefers to produce against the original strain are ‘mismatched’ for the new strain.

Meissner said, “To keep vaccinating with very similar [wuhan] antigens, may or may not be beneficial -- or the benefit may not outweigh the harm. I think we need to look at that.”

Since then, the data suggesting that immune imprinting is occurring, has only strengthened says Nikolai Petrovsky, Professor at Flinders University and developer of a protein-based covid-19 vaccine called SpikoGen® in use in Iran.

Prof Nikolai Petrovsky, Flinders University

“I feel the evidence for immune imprinting is increasingly compelling. It's a known phenomenon with flu where it was first described, and the data now suggests it’s happening with covid-19,” said Petrovsky.

“The omicron vaccines may struggle to switch the immune system of a heavily vaccinated person to making omicron-specific antibodies, as their immune system is so heavily biased toward the Wuhan spike protein in the original vaccines. In the end, this could be harder to achieve in a vaccinated person than someone who has not yet been exposed to any spike protein, for example, someone unvaccinated,” he added.

Petrovsky says not only do too many shots of the mRNA vaccines increase the risk of immune imprinting, but they also seem to be uniquely pushing the immune system into “tolerance” against the virus.

“Immune tolerance” occurs when the immune system becomes unresponsive to a particular antigen after repeated exposure. This is the principle for desensitising people to allergy, i.e. by repeatedly injecting them with small doses of the offending allergen over time.

Petrovsky points to a recent pre-print study out of Germany.  “People who've had three or more doses of mRNA showed a change in their antibodies to IgG4 which is typically an antibody associated with allergy desensitisation but not a normal antibody seen produced after infectious disease vaccines,” said Petrovsky.

Petrovsky said, “What this means, we simply don’t know as this has never been seen before.  That in itself is concerning as it indicates just how little we understand about what these new mRNA vaccines are doing and how they work. But to me, it raises a red flag that repeated doses of the mRNA vaccines might be driving immune tolerance against the virus. Maybe this could explain why the more doses of these vaccines, the less they seem to work, and more and more people are getting breakthrough infections?” Interestingly, the study did not find a similar shift in antibody patterns after AstraZeneca’s covid-19 vaccine.

Now, that the FDA has authorised the new bivalent boosters - which code for the original wuhan strain plus BA4/BA5 omicron lineages - without first requiring any human data to be collected, it has left many doubting that our public health authorities are even paying attention to the science.

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