When I look at the specification sheets for many of today's serology tests like the new Roche test or the Abbott test, they use a nucleocapsid antigen in the test, looking for anti-nucleocapsid antibodies. Given that these tests seem to have high sensitivities toward past infection, it suggests that recovered patients seem to reliably generate an immune response to the nucleocapsid.

At the same time, a lot of the research into vaccines focuses on the spike protein: Moderna is developing a vaccine based on an mRNA coding for the spike protein, CanSino and Oxford combine an adenovirus carrier with a SARS-CoV-2 spike, and so on. I'm having trouble finding any vaccines that target the nucleocapsid peptide.

I'm having trouble understanding this difference. Is it the case that recovered patients reliably produce antibodies to both viral components, but the nucleocapsid is better for testing due to cross-reactivity or other concerns? Or does a natural immune response target the nucleocapsid, while scientists think that the spike is a much better target because it's directly expressed on the cell surface or for some other reason?

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    $\begingroup$ N is highly antigenic because N-Elisa works and shows an early and high Ab load. N is hidden inside the virions and infected cells so it is unclear how anti-N Ab might be useful. The antigen presentation and B-cell maturation (as described in the books) doesn't depend on if targeting the antigen will be efficient. Emphasizing neutralizing antibodies is probably deserved but they are not all, most antibodies simply tag and opsonize the virions and infected cells for destruction by immune cells. S accumulates on the surface of virions and infected cells, a perfect marker $\endgroup$
    – reuns
    May 15, 2020 at 18:08

1 Answer 1


The vaccines will be directed towards a protein/epitope of the virus that creates the most robust immunogenic response, in which the defense system will create an array of antibodies to confer immunity, those antibodies will have to NEUTRALIZE the virus upon entry. In the case of SARS-CoV-2, the majority of research shows that neutralizing antibodies are directed towards the S1, S2 and RBD proteins which are all part of the S protein.

In this same line, the fact that the body creates antibodies directed towards other components of the virus doesn't mean that they are protective. So creating a vaccine towards those components wouldn't be useful at all.

The reason why those serologic tests target the N protein is probably due to the fact that is highly antigenic. But I'm sure I've seen tests that also target the S protein.

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    $\begingroup$ Can you please provide citations for the claims that (1) antibodies directed toward the S protein are neutralizing and (2) the N protein is highly antigenic? $\endgroup$
    – acvill
    May 15, 2020 at 14:15

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