Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice

Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice: iScience

​What does this paper say? What is it misused for?

The paper compares a vaccination series dose regime in young (6 weeks old) mice, which is 4 dosages, with a 6 dosage regime; all within 6 or 12 weeks respectively, with a RBD protein vaccine.

1) this is in young mice
2) this is a high frequency dosing regime, used for the induction of immune tolerance, such as to counter allergies
3) a specific adjuvant (to increase immune system response): Complete Freund's Adjuvant (CFA), which consists of heat-killed Mycobacterium tuberculosis in non-metabolizable oils (paraffin oil and mannide monooleate). This is forbidden to be used in humans. 

If you use such a high and strong vaccine frequency in mice, the response flattens a bit at the end.

The consequence of very short intervals between injections with RBD protein (which is reminiscent of a tolerance protocol) is reduced neutralization and antibody production. The reason is suppression of the Germinal Centre (GC) reaction. The GC reaction is the follicle where B and T cells meet; where T cells provide help to B cells to make more and better antibodies, and to assist to mature/improve those antibodies.

The reduced response is also seen in the very recently activated (CD69+) T cell compartment; CD4 T cells that help B cells make and mature antibodies, are reduced. This does not show total T cells, but cell expressing the temporal activation marker CD69 in secondary lymphoid organs and blood: this is very transiently expressed. With n=3, the strength and the relevance is not clear.

Please note;
- These are young mice
- This is a very short succession, without time to mature, between vaccines
- This is the protein vaccine
- No we don't see this after 3 or 4 dosages of vaccines in human; that is why we space them!
- This is a very strong adjuvant forbidden to be used in humans
- We see very high antibody levels after the 4th vaccine in humans with very good protection
- We see very good neutralising antibody levels, that improve after 3 and 4 dosages
- We see the clinical reduction of infections and disease as a result of vaccinations: they work very well!
- This is a protocol used for inducing tolerance, such as against allergens
- Indeed, multiple boosters in short succession (within weeks) should not be used, and is not used.

Current state of vaccinations required;
- 3x vaccination is sufficient to protect against disease in non-vulnerable people
- 4x, and possibly annually prior to viral season like the influenza vaccines, is required for more vulnerable groups. This paper does certainly not suggest that you shouldn't do that or that it is harmful!!