Follmann et al.: "Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial"

'Seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% [95% CI, 27% to 54%]) versus 605 of 648 placebo recipients (93% [CI, 92% to 95%]).'

Another win for natural immunity (we had this as pre-print but now published in peer reviewed journal).

This is a major concern if the mRNA vaccine is impacting N Ab inducement, for then the unvaccinated who are naturally exposed and infected and mount an immune response, will show a far superior and broad immune response that includes Ab to not only the mutable spike but also to other viral proteins such as the interior nucleocapsid protein (evidence of long-term acquired-adaptive natural immunity). 

‘Antibodies against the nucleocapsid protein (anti-N Abs) are not elicited by COVID-19 vaccines that target the spike protein, including all vaccines currently used in the United States. '

Bottom line: only 40% mRNA vaccine recipients developed anti-N Ab compared to 90% of placebo recipients.

SOURCE:

https://www.acpjournals.org/doi/10.7326/M22-1300

Aim:

To evaluate anti-nucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.

Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial.

99 sites in the United States, July 2020 through March 2021.

Participants were aged 18 years or older, had no known history of SARS-CoV-2 infection, and were at risk for SARS-CoV-2 infection or severe COVID-19.

Among 812 participants with PCR-confirmed COVID-19 illness during the blinded phase of the trial (through March 2021), seroconversion to anti-N Abs (median of 53 days after diagnosis) occurred in 21 of 52 mRNA-1273 vaccinees (40% [95% CI, 27% to 54%]) versus 605 of 648 placebo recipients (93% [CI, 92% to 95%]). Each 1-log increase in SARS-CoV-2 viral copies at diagnosis was associated with 90% higher odds of anti-N Ab seroconversion (odds ratio, 1.90 [CI, 1.59 to 2.28]).

Substantially less N Ab (nucleocapsid antibodies are highly conserved and stable, unlike the mutable spike protein) emerged in the vaccinated than those who were unvaccinated.  Prior mRNA-1273 vaccination influenced/impacted anti-nucleocapsid antibody seroconversion relative to those unvaccinated.

I had included this piece on natural immunity in the seminal op-ed that is iterating as new studies emerge but it was pre-print then and not yet peer-reviewed: