Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination
I picked it up via a tweet from Gabor Erdosi in the aftermath of the excellent discussion he had with Raphi, available on Youtube.
The only fundamental problem I have with their discussion was about original antigenic sin and the above pertains directly to this.
I was very pleased to receive the OAS source paper from Mike Eades (thanks Mike!) and it's a great read. An old paper from 1960, written in the style of the time, giving a basic idea discussed in almost conversational terms by a single author, with enough data to back up the idea, explaining where it came from. I can't see the original paper on tinternet although there are lots citing it:
ON THE DOCTRINE OF ORIGINAL ANTIGENIC SIN
EDIT location for the first page provided via eugyppius END EDIT
NEXT EDIT Full text here, thanks to Raphi END EDIT AGAIN
So. My fundamental difference in viewpoint to Gabor is that my expectation is that OAS from the mRNA vaccines would be limited to the systemic immune system and the respiratory mucosal immune system would be free from OAS and so able to mount a broad, effective response to produce sterilising immunity to a field infection. Whatever the evolution of spike protein to antibody avoidance, the respiratory mucosal system should stay clean.
So. My fundamental difference in viewpoint to Gabor is that my expectation is that OAS from the mRNA vaccines would be limited to the systemic immune system and the respiratory mucosal immune system would be free from OAS and so able to mount a broad, effective response to produce sterilising immunity to a field infection. Whatever the evolution of spike protein to antibody avoidance, the respiratory mucosal system should stay clean.
The above technique of giving an intranasal live attenuated influenza vaccine at the same time as a systemic IgG inducing mRNA based vaccine appears to trigger respiratory mucosal IgA formation to the systemic spike protein antigen. You "kick" the respiratory system with an attenuated influenza vaccine and the "awake" respiratory immune system "notices" and responds to what should have been a systemic-only spike protein stimulus.
In the UK we already have routine childhood intranasal influenza vaccines. I'm not anti-vax, my kids get the intranasal flu vaccine, FWIW. Assuming mRNA Covid vaccines are made mandatory for children (peak stupidity, but nothing surprises me) I can see that the logistics of delivering both vaccines on the same day might favour doing both at once.
So for kids OAS would be effectively extended from systemic IgG to mucosal IgA. Which might well blunt a correct, broad antigenic response within the airway at the time of a subsequent field virus infection.
This sounds like a very, very, very stupid thing to do.
So it will probably become standard practice, even mandatory.
Peter
On the plus side the mucosal IgA might be sterilising, if anti-spike antibodies are enough to kill all of the virus. This will limit time available for selecting an anti-spike antibody evading strain of virus. But the pressure will be still there.
It's like giving a full therapeutic dose of methicillin to a patient with a methicillin susceptible staphylococcal infection. It works. You have to do it. You have to kill the staph completely. But one day you will still successfully select for MRSA... It will happen. It already has.
