Nothing in this post should be seen as supporting an anti-vaccination viewpoint. If you see it that way, you are wrong. Contact me at virusquestions google mail if you disagree AND are up for civilized, reasonable conversation about this.
I’m in the process of making a video explaining ELISAs and as usual, I am in an interesting rabbit hole. I found a 2008 paper (1) focusing on the role of complement in anti-viral immunity that has an ELISA in it – last week’s unit went over complement, so it kills two birds with one… whatever. The rabbit hole comes from the fact that its looking at Mumps Virus, which happens to be part of a side-quest I’m on. It also gets at some questions that areb in the air a lot these days related to how antibodies work.
They look at how serum (that’s the liquid part of the blood minus the cells) from 10 normal donors (so, not infected) neutralizes 3 different viruses: mumps virus, human parainfluenza type 2 virus (HPIV2) and simian virus 5. All three are paramyxoviruses but only the first 2 would I expect humans to have encountered. Using ELISA they show that all 10 have antibodies to all three viruses – the antibodies to SV5 were most likely generated to related viruses (like mumps) and are cross reacting.
I don’t have time to write a figure by figure account, so basically, they look at how the sera from these donors neutralizes each of these viruses. Basically this involves incubating a certain amount of the virus with a little bit of the sera, then testing to see how much that virus replicates. I think most people think that the antibodies stick to and kill the virus and that’s the end of that; if so they are wrong. While antibodies are critical for neutralization of HPIV2, apparently they are NOT critical for the neutralization of MuV or SV5..this is done by heating the serum at a temperature that does not kill the antibodies but does kill complement proteins. In the case of both MuV and SV5, heating almost totally prevents the serum from neutralizing the virus.
They do some more experiments to show that MuV and SV5 are being killed by the alternative pathway of complement activation, but I want to skip to the end, where they show that complement is causing intact SV5 particles to aggregate into huge clumps (which apparently complement also does to influenza virus) whereas it’s actually lysing (poking holes in, destroying) the mumps virions.
So its kind of like someone inactivated the cash in your wallet by gluing all the kills together (no one would accept that as payment) or ripping your bills into pieces.
Also, no one should walk away from this thinking that they don’t need antibodies to mumps virus. While complement is an important part of all immune responses, clearly it is not enough to prevent people from getting infected – before vaccination for mumps there were hundreds of thousands of infections each year – all of those infected people had complement in their serum.
Interestingly, all of the donors had a lower titer of antibodies to MuV than to HPIV2. HPIVs (there are 4) are the second most common cause of acute respiratory-illness hospitalizations in children under 5, but it does infect other age groups and has a peak of infections roughly every Fall/Winter (2) They don’t say anything about the donors other than that they were “healthy adults” ….mumps vaccination status might have been interesting. One possibility here is that these 10 donors had more recent exposure to one of the HPIVs, thus explaining the higher antibody titer compared to MuV, and lacking those antibodies only complement is left to neutralize virus.
References
(1) Johnson et al 2008 Virology. Differential mechanisms of complement-mediated neutralization of the closely
related paramyxoviruses simian virus 5 and mumps virus
(2) DeGroote et al 2020 J. Clin. Virology. Human parainfluenza virus circulation, United States, 2011-2019