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If one person gets an mRNA vaccine that teaches their body to deal with a specific virus, and another person gets a similar but different mRNA vaccine, and another person gets a more "classic" vaccine with modified/weakened/dead virus cells, will there be any real difference in the antibodies developed by the three different people?

My gut instinct says that the antibodies/proteins developed by all of the people will be mostly identical, but I'm not a biologist.

I'm having difficulty finding articles/research on this. Full disclosure: this somewhat pertains to the SARS-CoV-2 and the varying vaccines, but it is also a more general question. I was hoping to find research on this, but it is proving difficult to google for such a verbose subject.

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    $\begingroup$ The mRNA may encode different antigenes, e.g. different parts of SARS-CoV-2's spike protein, or other parts of its membrane or hull. See nature.com/articles/s41422-020-00392-7. The immune response will/would differ accordingly even in the same individual. Obviously, inactivated viruses will expose several proteins, but not in isolation, and have a different response yet. $\endgroup$
    – Peter - Reinstate Monica
    Apr 15, 2021 at 11:16
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    $\begingroup$ In the COVID-19 pandemic, there has been some discussion on the effectiveness when people receive the first dose with one vaccine an the second dose with a different one. $\endgroup$
    – gerrit
    Apr 16, 2021 at 7:13
  • $\begingroup$ "differing vaccines" - Do they differ? All Covid-19 vaccines seem to code for the same spike, in full length (m-RNA- and vector-vaccines only differ in their being based on either RNA or DNA), and differences if there are pertain to coding specific promoting oder stop codons only? And even protein vaccines do not differ in that respect. Don't they all use the same spike antigen with all its epitopes? $\endgroup$
    – Peter Bernhard
    May 2, 2021 at 13:31

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Due to the nature of the immune system, even people who receive the same vaccine will have a different set of antibodies.

Our immune systems generate a vast number of essentially random recognition combinations, unique to every individual. This leads to a polyclonal response to both infections and vaccines, involving multiple antibodies and the fine details of those antibodies differ based on the specific antibodies in the "library" that the person's body has generated.

Now, different antigens do result in different antibodies being selected for, so one might expect there to be additional differences due to getting an mRNA coding for a SARS-CoV-2 spike protein vs. getting a whole inactivated virus. There's a reason that the spike protein is the preferred target, however, in that its position on the outside of the virus leads it to be a focal point for the response to an inactivated virus.

Bottom line: the responses will differ, but will likely always have a varied set of antibodies targeting the spike protein in any case.

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    $\begingroup$ Great answer! I have a question. Won't all antibodies be targeted to antigens on the surface of the protein? Is it possible / useful for an antigen to bind to other types of proteins? $\endgroup$
    – gardenhead
    Apr 15, 2021 at 14:26
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    $\begingroup$ Antibodies do show up against non-structural proteins as well (e.g., ncbi.nlm.nih.gov/pmc/articles/PMC2812099). I believe this is more significant for antigen presentation, whereas the surface proteins are more significant for neutralization of extracellular viruses. $\endgroup$
    – jakebeal
    Apr 15, 2021 at 15:14
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    $\begingroup$ Do the antibody tests just look at common antibodies that should be shared across almost almost individuals who have developed a resistance to the virus? Even when the tests work as desired, could they still miss resistance in a person who has different antibodies for Sars-Cov-2 than the ones being tested for? If so, is this a common issue? $\endgroup$
    – tparker
    Apr 17, 2021 at 17:06
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    $\begingroup$ @tparker Antibody tests don't actually check for specific antibodies. Instead, they present pieces of the antigen (in this case, various fragments of SARS-CoV-2 virus) and measure how many antibodies in a person's blood will bind to them. $\endgroup$
    – jakebeal
    Apr 17, 2021 at 19:01
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    $\begingroup$ @PeterBernhard That sounds like a whole new question or two to ask... $\endgroup$
    – jakebeal
    May 2, 2021 at 18:35

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