The history of failed HIV vaccine trials confirms that overvaccination causes class-switching towards non-inflammatory IgG4 antibodies, reducing the effectiveness of the immune response

Our mRNA Covid vaccines have caused exactly the same IgG4 class-switch, presumably in billions, whose immune systems have similarly been taught some measure of tolerance towards the spike protein

I am more and more convinced that the class-switch towards non-inflammatory IgG4 antibodies after repeated mRNA vaccination is a bad thing. It also seems pretty clear that immunologists know it’s a bad thing, because they admit as much in other contexts.

Inspired by this tweet, I’ve spent the afternoon reading up on HIV-1 vaccine trials, specifically the RV 144 trial conducted between 2003 and 2006 in the wake of the failed VAX003 trial, conducted between 1999 and 2003. Both trials were conducted in Thailand.

In the VAX003 trial, participants received seven (!) doses of AIDSVAX B/E, a vaccine consisting of a modified version of the HIV protein known as gp120, with an adjuvant. At the end, vaccinees did no better against infection than those who received placebos.

In the RV 144 trial, participants received four doses of ALVAC HIV (vCP1521), a vector vaccine coding for the Gag, Pol and Env proteins. The last two of these four injections were given alongside the AIDSVAX B/E vaccine from the VAX003 trial. This time, the six-injection ALVAC/HIV and AIDSVAX B/E regimen yielded a 31% protection against infection, becoming the first HIV vaccine trial to show any efficacy.

I don’t think anyone would call RV 144 a success, but it’s clear that VAX003 was a failure, and one reason seems to be overvaccination, causing a class switch from IgG3 to IgG4 non-neutralising antibodies. In VAX003, they administered so many injections targeting a single protein (sound familiar?) that they essentially taught the immune systems of vaccinees to tolerate that protein. In the RV 144 trial, meanwhile, they targeted a wider range of virus proteins, each with fewer doses.