Sin to the original antigen

Covid-19: The new wave of Omicron infections does not provide much immunity to those vaccinated against that variant and elicits a very attenuated antibody response in general because the severity is mild.

Santo Domingo, DR
Let me explain why some booster doses, or “boosters” as they are called, are not up to par with what we expect.

The new wave of Omicron infections does not provide much immunity to those vaccinated against that variant and causes a very attenuated antibody response because the severity is mild. This is not a specific effect of Omicron; humans are continually reinfected with many benign respiratory viruses, presumably because mild infections induce only a mild level of immunity.

For example, if monkeys are vaccinated against the original type SARS-2 strain, the one we know as “alpha,” and then injected with a booster of the Omicron-type SARS-2 strain, they develop a more effective antibody response to the Omicron variant than monkeys receiving Omicron-specific boosters.

This phenomenon is known as “Sin to the Original Antigen.”

The observation that booster with mRNA-1273 or Omicron mRNA resulted in the expansion of an equally high frequency of cross-reactive B cells probably derives from the principle of original antigenic sin, also called “antigenic imprinting,” whereby the memory of the previous immune system is recalled by a related antigenic encounter.

Therefore, the concern is whether a booster with a heterologous vaccine matching the dominant circulating variant has added value or whether the cross-reactive B-cell recalls immunity obtained by a booster with the original vaccine is sufficient to reduce infection and the level of disease severity.

If Omicron variant-specific vaccines only protect against Omicron infection, Omicron-specific vaccines are useless at best. At worst, they will be less effective in eliciting cross-responses to older vaccines.

Going forward, if Omicron, or a similar variant, continues to prevail for some years, a change in the initial vaccination regimen may be warranted, especially in immunologically naïve populations such as children. First, however, a change in COVID-19 vaccine design would have to be established to accommodate the current dominant variant that would not jeopardize responses against variants that may be antigenically distant from Omicron but, in turn, close to the prototype.

Put more simply: We vaccinate billions of people and imprint in their immune systems the protein of the original SARS-2 strain, which is now extinct, and hope to immunize billions more against this still obsolete protein so that their immune systems will also focus on this obsolete strain.

We equally want to vaccinate children against the original type of virus in its entirety and make sure that their immune systems focus on this obsolete protein indefinitely.

We should be VERY careful about making similar mistakes in the future. If we vaccinate children against Omicron alone, other variants could take advantage of their immune systems, which is precisely what is happening now with the population with regard to Omicron.

Using the virus strain protein was the worst thing to do, as the strain changes the most over time as the virus evolves, which it does, regardless of what the human race does or does not do to combat this pandemic.

All four mRNA/DNA vaccines encode only the strain protein, yet they wonder why the efficacy declines rapidly. In addition, the more hardened you are, the more susceptible you are to becoming infected or reinfected with SARS-CoV-2.

At this level, one can only conclude without evidence that this targeting strategy was only done inadvertently, not to refer to its intentionality.

In summary, this article proposes the dilemma of what the second generations of COVID vaccines should look like. Its theme is Sin to the Original Antigen. This means whether vaccines should cover only the current variants such as Omicron 1, 2, 4, 5, and Omicron Recombinant XAG, or should they never allow the original lethal versions such as Alpha, and the aggressive Delta, to re-emerge.

—Dr. José R. Yunén