Antibodies In opposition to SARS-CoV-2 Nucleocapsid Protein Might Not Be Dependable Markers for An infection in Vaccinated Folks


by Gertrud U. Rey

You’re totally vaccinated in opposition to SARS-CoV-2 and have presumably by no means been contaminated with the virus. However how are you going to know for certain? One technique to discover out is by testing your blood for the presence of antibodies in opposition to the viral nucleocapsid protein, which might solely be encountered throughout pure an infection. It’s because all the SARS-CoV-2 vaccines used within the U.S. solely encode the viral spike protein (none encode nucleocapsid [N] protein), and thus they solely stimulate manufacturing of antibodies in opposition to spike. This strategy differentiates between vaccine- and virus infection-induced antibodies and permits one to precisely decide whether or not a vaccinated individual was naturally contaminated. Or so we thought till now.

Two latest letters to the editor of the Journal of An infection notice that not each pure an infection induces manufacturing of anti-nucleocapsid (or, “anti-N”) antibodies. The letters solid doubt on whether or not these antibodies are dependable markers for a previous SARS-CoV-2 an infection.

The authors of the primary letter measured antibody responses in 4,111 vaccinated and 974 unvaccinated Irish healthcare employees. Solely 23 of the vaccinated individuals, all of whom had obtained two doses of the Pfizer mRNA vaccine, skilled a SARS-CoV-2 an infection at a while after vaccination. As anticipated, every of the 23 people had antibodies in opposition to the spike protein, however surprisingly, solely six (26%) had detectable anti-N antibodies. In distinction, 82% of unvaccinated individuals with a earlier PCR-confirmed an infection had detectable anti-N antibodies. This outcome means that anti-N antibodies might not be probably the most correct indicators of a previous pure an infection in vaccinated folks; and it additional implies that vaccinated people might neutralize incoming viruses early throughout an infection, thus stopping and/or limiting their potential to develop antibodies in opposition to nucleocapsid protein.

The second letter, which was written in response to the primary letter, confirmed and additional substantiated these outcomes. Citing information from serosurveys completed in Japan, the authors confirmed that sufferers who had been contaminated inside two months of a 3rd dose of the Pfizer mRNA vaccine had been much less prone to expertise COVID-19 signs than sufferers who had been contaminated 4-8 months after the third dose. These findings are in keeping with our present understanding of sterilizing immunity, a sort of immunity that forestalls each illness and an infection, which seems to happen most frequently through the months following vaccination, when excessive ranges of vaccine-induced antibodies in all probability sequester an incoming virus earlier than it has an opportunity to contaminate cells. The authors additionally confirmed that individuals contaminated inside two months of their third vaccine dose had considerably decrease ranges of anti-N antibodies than these contaminated a number of months later. Though this outcome appears stunning at first, it truly additional helps the notion that vaccination solely induces sterilizing immunity for a short while after vaccination, when current vaccine-induced anti-spike antibodies neutralize incoming virus earlier than the immune system has an opportunity to answer the virus and produce antibodies particular to the nucleocapsid protein.

The authors of each letters additional point out that COVID-19 sufferers who skilled signs had been extra prone to have detectable anti-N antibodies than had been sufferers with out signs, an commentary that’s in settlement with serological surveys completed earlier than vaccines turned out there. This discovering means that sufferers who developed signs didn’t have sterilizing immunity and had been topic to a productive viral an infection that led to the event of signs and manufacturing of antibodies to nucleocapsid and different viral proteins.

These two research present an attention-grabbing perspective of antibody responses to SARS-CoV-2 an infection in vaccinated folks, they usually might inform higher methods for gauging an infection after vaccination.


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