mRNA injections may reduce the ability to produce a key type of antibody

Anti-nucleocapsid antibodies following SARS-CoV-2 infection in the blinded phase of the mRNA-1273 Covid-19 vaccine efficacy clinical trial – doi: https://doi.org/10.1101/2022.04.18.22271936

Coronavirus injections may affect the body’s ability to produce a key type of antibody, which could limit the immune system’s defences against mutated strains of the virus, a new study suggests. Trial participants who received the placebo, rather than the injection, and became infected during the trial were found to have significantly higher levels of neutralising anti-nucleocapsid antibodies than vaccinated participants who had comparable viral loads. And that approximately 60% of participants in the placebo cohort who experienced very mild infection, with low viral loads, had anti-nucleocapsid antibodies, compared to approximately 10% of vaccinated subjects.

The study is based on data collected during Moderna’s randomised control trial for its SARS-CoV-2 mRNA vaccine, from July 2020 to March 2021.

The researchers looked at participants who tested positive for the coronavirus during the trial, comparing serum levels of specific types of antibodies, according to vaccination status, as well as viral load.

In particular, the study looks at the antibody response to the nucleocapsid core protein of the virus, using anti-nucleocapsid antibody (abs anti-N) levels as a marker of the immune system’s comprehensive response to the virus, as opposed to the more limited response to the spike protein. SARS-CoV-2 variants with mutated spike proteins have been of concern because of the dependence of injection immunity on antibodies directed to the s-proteins of the original variant.

As expected, serum levels of anti-nucleocapsid antibodies varied according to the viral load measured in the placebo and vaccine cohorts, and participants with higher viral loads were found to have higher levels of neutralising anti-nucleocapsid antibodies.

However, the researchers also found a pronounced difference in anti-nucleocapsid antibody levels between vaccinated participants and members of the placebo cohort, even when the study controlled for viral load.

Trial participants who received the placebo, rather than the injection, and became infected during the trial were found to have significantly higher levels of neutralising anti-nucleocapsid antibodies than vaccinated participants who had comparable viral loads.

Approximately 60% of participants in the placebo cohort who experienced very mild infection, with low viral loads, were found to have anti-nucleocapsid antibodies, compared to approximately 10% of vaccinated subjects.

Among those with higher viral loads, who qualify as mild, rather than very mild cases, 71% of the unvaccinated developed anti-nucleocapsid antibodies, compared to only 15% of those in the vaccinated group.

Of all the unvaccinated subjects who had been diagnosed with the virus during the trial, almost all (93%) had measurable levels of anti-nucleocapsid antibodies, compared with less than half (40%) of those in the vaccinated cohort.

“While an increase in seroreversion cannot be ruled out, given the short time period, the most likely explanation is a reduction in injection-induced seroconversion,” the researchers wrote, suggesting that trial participants who received the injection had reduced levels of anti-nucleocapsid antibodies as a direct result of the vaccine’s limited focus on the spike protein.

The researchers also hinted that the decreased anti-nucleocapsid antibody response among vaccinees could lead to undercounting of breakthrough cases, when measured by antibody sampling.

“Even with frequent serological sampling, serological surveys that rely on antibodies to the N protein may underestimate transmission dynamics within the community”.

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